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Sample records for human nasal tissue

  1. Biomechanical characterisation of the human nasal cartilages; implications for tissue engineering.

    PubMed

    Griffin, M F; Premakumar, Y; Seifalian, A M; Szarko, M; Butler, P E M

    2016-01-01

    Nasal reconstruction is currently performed using autologous grafts provides but is limited by donor site morbidity, tissue availability and potentially graft failure. Additionally, current alternative alloplastic materials are limited by their high extrusion and infection rates. Matching mechanical properties of synthetic materials to the native tissue they are replacing has shown to be important in the biocompatibility of implants. To date the mechanical properties of the human nasal cartilages has not been studied in depth to be able to create tissue-engineered replacements with similar mechanical properties to native tissue. The young's modulus was characterized in compression on fresh-frozen human cadaveric septal, alar, and lateral cartilage. Due to the functional differences experienced by the various aspects of the septal cartilage, 16 regions were evaluated with an average elastic modulus of 2.72 ± 0.63 MPa. Furthermore, the posterior septum was found to be significantly stiffer than the anterior septum (p < 0.01). The medial and lateral alar cartilages were tested at four points with an elastic modulus ranging from 2.09 ± 0.81 MPa, with no significant difference between the cartilages (p < 0.78). The lateral cartilage was tested once in all cadavers with an average elastic modulus of 0.98 ± 0.29 MPa. In conclusion, this study provides new information on the compressive mechanical properties of the human nasal cartilage, allowing surgeons to have a better understanding of the difference between the mechanical properties of the individual nasal cartilages. This study has provided a reference, by which tissue-engineered should be developed for effective cartilage replacements for nasal reconstruction. PMID:26676857

  2. Characteristics of Nasal-Associated Lymphoid Tissue (NALT) and Nasal Absorption Capacity in Chicken

    PubMed Central

    Kang, Haihong; Yan, Mengfei; Yu, Qinghua; Yang, Qian

    2013-01-01

    As the main mucosal immune inductive site of nasal cavity, nasal-associated lymphoid tissue (NALT) plays an important role in both antigen recognition and immune activation after intranasal immunization. However, the efficiency of intranasal vaccines is commonly restricted by the insufficient intake of antigen by the nasal mucosa, resulting from the nasal mucosal barrier and the nasal mucociliary clearance. The distribution of NALT and the characteristic of nasal cavity have already been described in humans and many laboratory rodents, while data about poultry are scarce. For this purpose, histological sections of the chicken nasal cavities were used to examine the anatomical structure and histological characteristics of nasal cavity. Besides, the absorptive capacity of chicken nasal mucosa was also studied using the materials with different particle size. Results showed that the NALT of chicken was located on the bottom of nasal septum and both sides of choanal cleft, which mainly consisted of second lymphoid follicle. A large number of lymphocytes were distributed under the mucosal epithelium of inferior nasal meatus. In addition, there were also diffuse lymphoid tissues located under the epithelium of the concha nasalis media and the walls of nasal cavity. The results of absorption experiment showed that the chicken nasal mucosa was capable to absorb trypan blue, OVA, and fluorescent latex particles. Inactivated avian influenza virus (IAIV) could be taken up by chicken nasal mucosa except for the stratified squamous epithelium sites located on the forepart of nasal cavity. The intake of IAIV by NALT was greater than that of the nasal mucosa covering on non-lymphoid tissue, which could be further enhanced after intranasal inoculation combined with sodium cholate or CpG DNA. The study on NALT and nasal absorptive capacity will be benefit for further understanding of immune mechanisms after nasal vaccination and development of nasal vaccines for poultry. PMID

  3. Effects of Endogenous Formaldehyde in Nasal Tissues on Inhaled Formmaldehyde Dosimetry Predictions in the Rat, Monkey, and Human Nasal Passages

    EPA Science Inventory

    ABSTRACT Formaldehyde, a nasal carcinogen, is also an endogenous compound that is present in all living cells. Due to its high solubility and reactivity, quantitative risk estimates for inhaled formaldehyde rely on internal dose calculations in the upper respiratory tract which ...

  4. In vivo implantation of tissue engineered human nasal septal neocartilage constructs: a pilot study

    PubMed Central

    Chang, Angela A.; Reuther, Marsha S.; Briggs, Kristen K.; Schumacher, Barbara L.; Williams, Gregory M.; Corr, Maripat; Sah, Robert L.; Watson, Deborah

    2014-01-01

    Objective To determine the in vivo biocompatibility of septal neocartilage constructs developed in vitro by an alginate intermediate step. Study Design Prospective, animal model. Setting Research laboratory. Subjects and Methods A murine model was used to examine the maturation of neocartilage constructs in vivo. Chondrocytes collected from patients undergoing septoplasty were expanded in monolayer and suspended in alginate beads for three-dimensional culture in media containing human serum and growth factors. After in vitro incubation for 5 weeks, the constructs were implanted in the dorsum of athymic mice for 30 and 60 days (n=9). After the mice were sacrificed, the constructs were recovered for assessment of their morphological, histochemical, biochemical, and biomechanical properties. Results The mice survived and tolerated the implants well. Infection and extrusion were not observed. Neocartilage constructs maintained their general shape and size, and demonstrated cell viability after implantation. The implanted constructs were firm and opaque, sharing closer semblance to native septal tissue relative to the gelatinous, translucent pre-implant constructs. Histochemical staining with hematoxylin and eosin (H&E) revealed that the constructs exhibited distinct morphologies characteristic of native tissue, which were not observed in pre-implant constructs. DNA and type II collagen increased with duration of implantation, whereas type I collagen and glycoaminoglycans (GAG) decreased. Mechanical testing of a 60-day implanted construct demonstrated characteristics similar to native human septal cartilage. Conclusions Neocartilage constructs are viable in an in vivo murine model. The histologic, biochemical, and biomechanical features of implanted constructs closely resemble native septal tissue when compared to pre-implant constructs. PMID:22031592

  5. A hybrid CFD-PBPK model for naphthalene in rat and human with IVIVE for nasal tissue metabolism and cross-species dosimetry.

    PubMed

    Campbell, Jerry L; Andersen, Melvin E; Clewell, Harvey J

    2014-05-01

    A PBPK model for naphthalene in the rat and human that incorporates a hybrid CFD-PBPK description of the upper respiratory tract was developed to support cross-species dosimetry comparisons of naphthalene concentrations and tissue normalized rate of metabolism in the nasal respiratory and olfactory epithelium, lung and liver. In vitro measurements of metabolic rates from microsomal incubations published for rat and monkey (surrogate for human) were scaled to the specific tissue based on the tissue microsomal content and volume of tissue. The model reproduces time courses for naphthalene blood concentrations from intravenous and inhalation exposures in rats and upper respiratory tract extraction data in both naïve rats and rats pre-treated to inhibit nasal metabolism. This naphthalene model was applied to estimate human equivalent inhalation concentrations (HECs) corresponding to several NOAELs or LOAELs for the non-cancer effects of naphthalene in rats. Two approaches for cross-species extrapolation were compared: (1) equivalence based on tissue naphthalene concentration and (2) equivalence based on amount metabolized per minute (normalized to tissue volume). At the NOAEL of 0.1 ppm, the regional gas dosimetry ratio (RGDR) based on naphthalene concentration was 0.18 for the dorsal olfactory region; however, the RGDR rises to 5.4 when based on the normalized amount metabolized due to the lower of expression of CYP isozymes in the nasal epithelium of primates and humans. The resulting HEC is 0.12 ppm (0.63 mg/m(3)) continuous exposure at the rat NOAEL of 0.1 ppm (6 h/day, 5 days/week). PMID:24666369

  6. Nasal soft tissue trauma and management.

    PubMed

    Immerman, Sara; Constantinides, Minas; Pribitkin, Edmund A; White, W Matthew

    2010-12-01

    The nose is the most prominent of all facial structures and is susceptible to many types of trauma. All soft tissue injuries of the nose have the potential to distort its appearance and adversely affect the patient's self-image and self-esteem. Once life-threatening injuries are stabilized, a careful history and physical exam should be completed and treatment individualized. The ultimate objective of treatment is to achieve both functional and cosmetic restoration with timely diagnosis and repair. Immediate nasal reconstruction is ideal when medically possible because this decreases long-term sequelae. PMID:21086240

  7. Nasal cytochrome P4502A: Identification in rats and humans

    SciTech Connect

    Thornton-Manning, J.R.; Hotchkiss, J.A.; Ding, Xinxin

    1995-12-01

    The nasal mucosa, the first tissue of contact for inhaled xenobiotics, possesses substantial enobiotic-metabolizing capacti. Enzymes of the nasal cavity may metabolize xenobiotics to innocuous, more water-soluble compounds that are eliminated from the body, or they may bioactivate them to toxic metabolites. These toxic metabolites may find to cellular macromolecules in the nasal cavity or be transported to other parts of the body where they may react. Nasal carcinogenesis in rodents often results from bioactivation of xenobiotics. The increased incidences of nasal tumors associated with certain occupations suggest that xenobiotic bioactivation may be important in human nasal cancer etiology, as well. The increasing popularity of the nose as a route of drug administration makes information concerning nasal drug metabolism and disposition vital to accomplish therapeutic goals. For these reasons, the study of xenobiotic-met abolizing capacity of the nasal cavity is an important area of health-related research. In the present study, we have confirmed the presence of CYP2A6 mRNA in human respiratory mucosa.

  8. Exploring the bacterial assemblages along the human nasal passage.

    PubMed

    Wos-Oxley, Melissa L; Chaves-Moreno, Diego; Jáuregui, Ruy; Oxley, Andrew P A; Kaspar, Ursula; Plumeier, Iris; Kahl, Silke; Rudack, Claudia; Becker, Karsten; Pieper, Dietmar H

    2016-07-01

    The human nasal passage, from the anterior nares through the nasal vestibule to the nasal cavities, is an important habitat for opportunistic pathogens and commensals alike. This work sampled four different anatomical regions within the human nasal passage across a large cohort of individuals (n = 79) comprising individuals suffering from chronic nasal inflammation clinically known as chronic rhinosinusitis (CRS) and individuals not suffering from inflammation (CRS-free). While individuals had their own unique bacterial fingerprint that was consistent across the anatomical regions, these bacterial fingerprints formed into distinct delineated groups comprising core bacterial members, which were consistent across all four swabbed anatomical regions irrespective of health status. The most significant observed pattern was the difference between the global bacterial profiles of swabbed and tissue biopsy samples from the same individuals, being also consistent across different anatomical regions. Importantly, no statistically significant differences could be observed concerning the global bacterial communities, any of the bacterial species or the range of diversity indices used to compare between CRS and CRS-free individuals, and between two CRS phenotypes (without nasal polyps and with nasal polyps). Thus, the role of bacteria in the pathogenesis of sinusitis remains uncertain. PMID:27207744

  9. Cytotoxic effects of nasal buserelin on nasal mucosal tissue in rabbits.

    PubMed

    Oghan, Fatih; Apuhan, Tayfun; Terzi, Hakan; Kukner, Aysel; Coksuer, Hakan; Yılmaz, Fahrettin

    2012-07-01

    To investigate the cytotoxic effects of nasal buserelin on rabbit nasal mucosal tissue, twenty-four female rabbits were studied prospectively. The rabbits were divided into 4 groups including 6 rabbits. The rabbits' left noses were included in the all study groups: 150 μg/puff/day of buserelin acetate was administered topically twice daily during 21, 42 and 63 days. Saline was administered topically twice daily to the left nasal cavity in the control group. The nasal septal mucosal stripe tissue was carefully removed from underlaying cartilage after sedation. HE staining, Masson's trichrome, toluidine blue and TUNEL staining were used to evaluate mucosal changes. Each preparation was investigated via apoptotic cells, and they were accounted. Kruskal-Wallis test was used to evaluate nonparametric comparison of apoptotic cells. Mononuclear cells have been raised in the sub-epithelial connective tissue, nucleuses of epithelial cells in the apical region were pyknotic, and apoptotic cells were determined on 21-day group. In the 42-day group, nasal epithelial tissue was similar to 21-day group and epithelial cells including pyknotic nucleus were present in this group, too. In the 63-day group, epithelial cells were light colored. Venous sinuses in the sub-epithelial connective tissue were wide but not congested and not raised collagen filaments. In the intra-epithelial tissue, some of cells were TUNEL (+). Apoptotic cells were fewer in the control group according to 21-day group. In 42- and 63-day groups, these cells were fewer than in 21-day group. Numerical difference was present between the groups, but statistical significance was not found between the groups. We concluded that nasal buserelin cytotoxicity was not potent in the nasal cavity in rabbits. We use nasal buserelin in all indications with confidence. PMID:22160101

  10. Nasal drug delivery in humans.

    PubMed

    Bitter, Christoph; Suter-Zimmermann, Katja; Surber, Christian

    2011-01-01

    Intranasal administration is an attractive option for local and systemic delivery of many therapeutic agents. The nasal mucosa is--compared to other mucosae--easily accessible. Intranasal drug administration is noninvasive, essentially painless and particularly suited for children. Application can be performed easily by patients or by physicians in emergency settings. Intranasal drug delivery offers a rapid onset of therapeutic effects (local or systemic). Nasal application circumvents gastrointestinal degradation and hepatic first-pass metabolism of the drug. The drug, the vehicle and the application device form an undividable triad. Its selection is therefore essential for the successful development of effective nasal products. This paper discusses the feasibility and potential of intranasal administration. A series of questions regarding (a) the intended use (therapeutic considerations), (b) the drug, (c) the vehicle and (d) the application device (pharmaceutical considerations) are addressed with a view to their impact on the development of products for nasal application. Current and future trends and perspectives are discussed. PMID:21325837

  11. The Human Nasal Microbiota and Staphylococcus aureus Carriage

    PubMed Central

    Frank, Daniel N.; Feazel, Leah M.; Bessesen, Mary T.; Price, Connie S.; Janoff, Edward N.; Pace, Norman R.

    2010-01-01

    Background Colonization of humans with Staphylococcus aureus is a critical prerequisite of subsequent clinical infection of the skin, blood, lung, heart and other deep tissues. S. aureus persistently or intermittently colonizes the nares of ∼50% of healthy adults, whereas ∼50% of the general population is rarely or never colonized by this pathogen. Because microbial consortia within the nasal cavity may be an important determinant of S. aureus colonization we determined the composition and dynamics of the nasal microbiota and correlated specific microorganisms with S. aureus colonization. Methodology/Principal Findings Nasal specimens were collected longitudinally from five healthy adults and a cross-section of hospitalized patients (26 S. aureus carriers and 16 non-carriers). Culture-independent analysis of 16S rRNA sequences revealed that the nasal microbiota of healthy subjects consists primarily of members of the phylum Actinobacteria (e.g., Propionibacterium spp. and Corynebacterium spp.), with proportionally less representation of other phyla, including Firmicutes (e.g., Staphylococcus spp.) and Proteobacteria (e.g. Enterobacter spp). In contrast, inpatient nasal microbiotas were enriched in S. aureus or Staphylococcus epidermidis and diminished in several actinobacterial groups, most notably Propionibacterium acnes. Moreover, within the inpatient population S. aureus colonization was negatively correlated with the abundances of several microbial groups, including S. epidermidis (p = 0.004). Conclusions/Significance The nares environment is colonized by a temporally stable microbiota that is distinct from other regions of the integument. Negative association between S. aureus, S. epidermidis, and other groups suggests microbial competition during colonization of the nares, a finding that could be exploited to limit S. aureus colonization. PMID:20498722

  12. Toxicology of the nasal passages

    SciTech Connect

    Barrow, C.S.

    1986-01-01

    Contents of this work include: Comparative Anatomy and Function of the Nasal Passages; Light Microscopic Examination of the Rat Nasal Passages: Preparation and Morphologic Features; Histopathology of Acute and Subacute Nasal Toxicity; Pathology of Chronic Nasal Toxic Responses Including Cancer; Responses of the Nasal Mucociliary Apparatus to Airborne Irritants; Effects of Chemical Exposure on Olfaction in Humans, Possible Consequences of Cytochrome P-450-Dependent Monooxygenases in Nasal Tissues.

  13. Demonstration of carboxylesterase in cytology samples of human nasal respiratory epithelium

    SciTech Connect

    Rodgers, D.A.; Nikula, K.J.; Avila, K.

    1995-12-01

    The epithelial lining of the nasal airways is a target for responses induced by a variety of toxicant exposures. The high metabolic capacity of this tissue has been suggested to play a role in both protection of the airways through detoxication of certain toxicants, as well as in activation of other compounds to more toxic metabolites. Specifically, nasal carboxylesterase (CE) has been shown to mediate the toxicity of inhaled esters and acrylates by converting them to more toxic acid and alcohol metabolites which can be cytotoxic and/or carcinogenic to the nasal mucosa. Due to difficulties in extrapolating rodent models to human, new paradigms using human cells and tissues are essential to understanding and evaluating the metabolic processes in human nasal epithelium.

  14. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps.

    PubMed

    Kim, Dong-Young; Lee, Sun Hye; Carter, Roderick G; Kato, Atsushi; Schleimer, Robert P; Cho, Seong H

    2016-08-01

    Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs. PMID:27163839

  15. Marine Collagen Scaffolds for Nasal Cartilage Repair: Prevention of Nasal Septal Perforations in a New Orthotopic Rat Model Using Tissue Engineering Techniques

    PubMed Central

    Bermueller, Christian; Elsaesser, Alexander F.; Sewing, Judith; Baur, Nina; von Bomhard, Achim; Scheithauer, Marc; Notbohm, Holger; Rotter, Nicole

    2013-01-01

    Autologous grafts are frequently needed for nasal septum reconstruction. Because they are only available in limited amounts, there is a need for new cartilage replacement strategies. Tissue engineering based on the use of autologous chondrocytes and resorbable matrices might be a suitable option. So far, an optimal material for nasal septum reconstruction has not been identified. The aim of our study was to provide the first evaluation of marine collagen for use in nasal cartilage repair. First, we studied the suitability of marine collagen as a cartilage replacement matrix in the context of in vitro three dimensional cultures by analyzing cell migration, cytotoxicity, and extracellular matrix formation using human and rat nasal septal chondrocytes. Second, we worked toward developing a suitable orthotopic animal model for nasal septum repair, while simultaneously evaluating the biocompatibility of marine collagen. Seeded and unseeded scaffolds were transplanted into nasal septum defects in an orthotopic rat model for 1, 4, and 12 weeks. Explanted scaffolds were histologically and immunohistochemically evaluated. Scaffolds did not induce any cytotoxic reactions in vitro. Chondrocytes were able to adhere to marine collagen and produce cartilaginous matrix proteins, such as collagen type II. Treating septal cartilage defects in vivo with seeded and unseeded scaffolds led to a significant reduction in the number of nasal septum perforations compared to no replacement. In summary, we demonstrated that marine collagen matrices provide excellent properties for cartilage tissue engineering. Marine collagen scaffolds are able to prevent septal perforations in an autologous, orthotopic rat model. This newly described experimental surgical procedure is a suitable way to evaluate new scaffold materials for their applicability in the context of nasal cartilage repair. PMID:23621795

  16. Characterizing adult human nasal airway dimensions

    SciTech Connect

    Guilmette, R.A.; Griffith, W.C.

    1994-11-01

    Respiratory tract models used in calculating radiation dose from exposure to inhaled radioactive aerosols have only recently focused attention on the importance of the nasal airways (NAs). Because the NAs are the first tissues of the respiratory tract available for aerosol deposition in normally nose-breathing people, any deposition of aerosol in this anatomical structure will reduce the amounts available to be deposited in the remainder of the respiratory tract. Thus, uncertainties in estimating the deposition fractions in the NAs will propagate throughout the remainder of the respiratory tract, creating errors in the calculated dose estimates. Additionally, there is evidence that the NAs are also at risk for induction of cancer from exposure to certain occupational aerosols such as wood dust, leather dust, chromium, and nickel. The purpose of this investigation was to conduct an anatomical study to assess the variabilities in NA dimensions.

  17. Correlation of nasal geometry with aerosol deposition in human volunteers

    SciTech Connect

    Cheng, Yung-Seng; Simpson, S.Q.; Cheng, Kuo-His; Swift, D.L.; Yeh, Hsu-Chi; Guilmette, R.A.

    1994-11-01

    The nasal airways act as the first filter in the respiratory tract to remove very large or small particles, that would otherwise penetrate to the lower airways. Aerosol deposition data obtained with human volunteers vary considerably under comparable experimental conditions. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. Because there is no direct proof of this hypothesis, nasal deposition of ultrafine particles in human volunteers has been studied in our laboratory. Preliminary results obtained with four adult volunteers also vary considerably between subjects. The purpose of this part of the study was to establish a theoretical equation relating diffusional deposition in nasal airways to the geometrical dimensions of the individual nasal airways. This relationship was then applied to the experimental deposition data and measurement of airway morphometry for correlation.

  18. Air-conditioning in the human nasal cavity.

    PubMed

    Elad, David; Wolf, Michael; Keck, Tilman

    2008-11-30

    Healthy humans normally breathe through their nose even though its complex geometry imposes a significantly higher resistance in comparison with mouth breathing. The major functional roles of nasal breathing are defense against infiltrating particles and conditioning of the inspired air to nearly alveolar conditions in order to maintain the internal milieu of the lung. The state-of-the-art of the existing knowledge on nasal air-conditioning will be discussed in this review, including in vivo measurements in humans and computational studies on nasal air-conditioning capacity. Areas where further studies will improve our understanding and may help medical diagnosis and intervention in pathological states will be introduced. PMID:18565805

  19. The ontogeny of nasal floor shape variation in extant humans.

    PubMed

    Nicholas, Christina L; Franciscus, Robert G

    2014-11-01

    Variation in nasal floor topography has generated both neontological and paleontological interest. Three categories of nasal floor shape (Franciscus: J Hum Evol 44 (2003) 699-727) have been used when analyzing this trait in extant humans and fossil Homo: flat, sloped, and depressed (or "bi-level"). Variation in the frequency of these configurations within and among extant and fossil humans has been well-documented (Franciscus: J Hum Evol 44 (2003) 699-727; Wu et al.: Anthropol Sci 120 (2012) 217-226). However, variation in this trait in Homo has been observed primarily in adults, with comparatively small subadult sample sizes and/or large age gradients that may not sufficiently track key ontogenetic changes. In this study, we investigate the ontogeny of nasal floor shape in a relatively large cross-sectional age sample of extant humans (n = 382) ranging from 4.0 months fetal to 21 years post-natal. Results indicate that no fetal or young infant individuals possess a depressed nasal floor, and that a depressed nasal floor, when present (ca. 21% of the sample), does not occur until 3.0 years postnatal. A canonical variates analysis of maxillary shape revealed that individuals with depressed nasal floors were also characterized by relatively taller anterior alveolar regions. This suggests that palate remodeling at about 3.0-3.5 years after birth, under the influence of tooth development, strongly influences nasal floor variation, and that various aspects of dental development, including larger crown/root size, may contribute to the development of a depressed nasal floor. These results in extant humans may help explain the high frequency of this trait found in Neandertal and other archaic Homo maxillae. PMID:25043897

  20. Heavy metals in normal mucosa and nasal polyp tissues from Tunisian patients.

    PubMed

    Khlifi, Rim; Olmedo, Pablo; Gil, Fernando; Chakroun, Amine; Hammami, Boutheina; Hamza-Chaffai, Amel

    2015-01-01

    Despite growing evidence that bacteria, fungi, allergens, and superantigens play a prominent role in the pathophysiology of nasal polyps (NP), the exact cause of polyposis is still unknown. The etiology of NP is considered multifactorial. Until now, there is no information on the presence of heavy metals, such as cadmium (Cd), chromium (Cr), nickel (Ni), and arsenic (As) or of their role, in the pathogenesis of NP disease. In this study, concentrations of these four metals in tissue of NP were determined using Atomic Absorption Spectrometry. The Ni, Cr, and As levels in NP tissues were 2.1-, 3.2-, and 8.0-fold higher than those of normal mucosa (p < 0.05), respectively. A strong effect of cumulative smoking as expressed in the number of pack per year (PY), Ni, As, and Cd levels in NP tissue samples of patients ever-smokers (1-20 and >20 PY) are significantly higher than those of non-smokers (p = 0.006, 0.002, and < 0.001, respectively). The highest As concentrations among patients lived at polluted areas (1-25 and > 25 years) were observed in both nasal mucosa and NP tissues. The Ni and As in both nasal mucosa and NP tissues of patients occupationally exposed were significantly higher than non-exposed group. Cr and As levels were found to be associated with NP stage classification (p < 0.05). This is the first report to describe an association between concentrations of metals (Cr, As, and Ni) in human NP tissues and the risk of NP disease. Tissue metal levels have increased due to smoking, environmental, and occupational exposure. Therefore, heavy metal exposure may increase the risk of NP in the Tunisian population. The considerable risk in the category of highest cumulative exposure argues for an association between heavy metals exposure and nasal polyposis risk. Future investigations with larger samples should better elucidate this association. PMID:25081002

  1. Shape of the human nasal cavity promotes retronasal smell

    NASA Astrophysics Data System (ADS)

    Trastour, Sophie; Melchionna, Simone; Mishra, Shruti; Zwicker, David; Lieberman, Daniel E.; Kaxiras, Efthimios; Brenner, Michael P.

    2015-11-01

    Humans are exceptionally good at perceiving the flavor of food. Flavor includes sensory input from taste receptors but is dominated by olfactory (smell) receptors. To smell food while eating, odors must be transported to the nasal cavity during exhalation. Olfactory performance of this retronasal route depends, among other factors, on the position of the olfactory receptors and the shape of the nasal cavity. One biological hypothesis is that the derived configuration of the human nasal cavity has resulted in a greater capacity for retronasal smell, hence enhanced flavor perception. We here study the air flow and resulting odor deposition as a function of the nasal geometry and the parameters of exhalation. We perform computational fluid dynamics simulations in realistic geometries obtained from CT scans of humans. Using the resulting flow fields, we then study the deposition of tracer particles in the nasal cavity. Additionally, we derive scaling laws for the odor deposition rate as a function of flow parameters and geometry using boundary layer theory. These results allow us to assess which changes in the evolution of the human nose led to significant improvements of retronasal smell.

  2. Correlation between Nasal Microbiome Composition and Remote Purulent Skin and Soft Tissue Infections

    PubMed Central

    Johnson, Ryan C.; Ellis, Michael W.; Lanier, Jeffrey B.; Schlett, Carey D.; Cui, Tianyuan

    2014-01-01

    The incidence of skin and soft tissue infections (SSTIs) has increased dramatically over the past decade, resulting in significant morbidity in millions of otherwise healthy individuals worldwide. Certain groups, like military personnel, are at increased risk for SSTI development. Although nasal colonization with Staphylococcus aureus is an important risk factor for the development of SSTIs, it is not clear why some colonized individuals develop disease while others do not. Recent studies have revealed the importance of microbial diversity in human health. Therefore, we hypothesized that the nasal microbiome may provide valuable insight into SSTI development. To examine this hypothesis, we obtained anterior-naris samples from military trainees with cutaneous abscesses and from asymptomatic (non-SSTI) participants. We also obtained samples from within abscess cavities. Specimens were analyzed by culture, and the microbial community within each sample was characterized using a 16S sequencing-based approach. We collected specimens from 46 non-SSTI participants and from 40 participants with abscesses. We observed a significantly higher abundance of Proteobacteria in the anterior nares in non-SSTI participants (P < 0.0001) than in participants with abscesses. Additionally, we noted a significant inverse correlation between Corynebacterium spp. and S. aureus (P = 0.0001). The sensitivity of standard microbiological culture for abscesses was 71.4%. These data expand our knowledge of the complexity of the nasal and abscess microbiomes and potentially pave the way for novel therapeutic and prophylactic countermeasures against SSTI. PMID:25486991

  3. Acid and Base Secretion in Freshly Excised Nasal Tissue From Cystic Fibrosis Patients with ΔF508 Mutation

    PubMed Central

    Cho, Do-Yeon; Hwang, Peter H.; Illek, Beate; Fischer, Horst

    2011-01-01

    Cystic fibrosis (CF) is caused by a misfunctional CFTR protein, which is believed to contributes to the regulation of the airway surface liquid (ASL) pH. This study investigated acid and base secretion in freshly excised human nasal tissues from CF patients homozygous for the ΔF508 mutation. Human nasal mucosa was collected during sinus surgery and investigated in Ussing chambers. Mucosal equilibrium pH values and rate of acid and base secretion were determined using the pH-stat technique. The equilibrium pH of nasal epithelia from ΔF508 CF patients with chronic rhinosinusitis (CRS) was pH = 7.08 ± 0.09 and significantly lower compared to nasal epithelia from CRS without CF (pH = 7.33 ± 0.06) and normal subjects (pH = 7.34 ± 0.08, n = 6). The rate of base secretion in CF nasal tissues was 11.8 ± 2.4 nmol·min−1·cm−2, which was significantly lower than normal (57.2 ± 9.2 nmol·min−1·cm−2). HCO3−secretory rate was further increased by forskolin by 16.1% in normal, but not in CF tissues. Our data suggests that CF patients exhibited significantly lower base secretion by the nasal airway epithelium. It is possible that improper regulation of ASL pH in CF may negatively impact the innate host defense system. PMID:22034590

  4. Testing gene therapy vectors in human primary nasal epithelial cultures

    PubMed Central

    Cao, Huibi; Ouyang, Hong; Ip, Wan; Du, Kai; Duan, Wenming; Avolio, Julie; Wu, Jing; Duan, Cathleen; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Hu, Jim; Moraes, Theo J

    2015-01-01

    Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for a chloride/bicarbonate channel in the apical epithelial membranes. CFTR dysfunction results in a multisystem disease including the development of life limiting lung disease. The possibility of a cure for CF by replacing defective CFTR has led to different approaches for CF gene therapy; all of which ultimately have to be tested in preclinical model systems. Primary human nasal epithelial cultures (HNECs) derived from nasal turbinate brushing were used to test the efficiency of a helper-dependent adenoviral (HD-Ad) vector expressing CFTR. HD-Ad-CFTR transduction resulted in functional expression of CFTR at the apical membrane in nasal epithelial cells obtained from CF patients. These results suggest that HNECs can be used for preclinical testing of gene therapy vectors in CF. PMID:26730394

  5. Testing gene therapy vectors in human primary nasal epithelial cultures.

    PubMed

    Cao, Huibi; Ouyang, Hong; Ip, Wan; Du, Kai; Duan, Wenming; Avolio, Julie; Wu, Jing; Duan, Cathleen; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Hu, Jim; Moraes, Theo J

    2015-01-01

    Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for a chloride/bicarbonate channel in the apical epithelial membranes. CFTR dysfunction results in a multisystem disease including the development of life limiting lung disease. The possibility of a cure for CF by replacing defective CFTR has led to different approaches for CF gene therapy; all of which ultimately have to be tested in preclinical model systems. Primary human nasal epithelial cultures (HNECs) derived from nasal turbinate brushing were used to test the efficiency of a helper-dependent adenoviral (HD-Ad) vector expressing CFTR. HD-Ad-CFTR transduction resulted in functional expression of CFTR at the apical membrane in nasal epithelial cells obtained from CF patients. These results suggest that HNECs can be used for preclinical testing of gene therapy vectors in CF. PMID:26730394

  6. The morphological interaction between the nasal cavity and maxillary sinuses in living humans.

    PubMed

    Holton, Nathan; Yokley, Todd; Butaric, Lauren

    2013-03-01

    To understand how variation in nasal architecture accommodates the need for effective conditioning of respired air, it is necessary to assess the morphological interaction between the nasal cavity and other aspects of the nasofacial skeleton. Previous studies indicate that the maxillary sinuses may play a key role in accommodating climatically induced nasal variation such that a decrease in nasal cavity volume is associated with a concomitant increase in maxillary sinus volume. However, due to conflicting results in previous studies, the precise interaction of the nasal cavity and maxillary sinuses, in humans, is unclear. This is likely due to the prior emphasis on nasal cavity size, whereas arguably, nasal cavity shape is more important with regard to the interaction with the maxillary sinuses. Using computed tomography scans of living human subjects (N=40), the goal of this study is to assess the interaction between nasal cavity form and maxillary sinus volume in European- and African-derived individuals with differences in nasal cavity morphology. First, we assessed whether there is an inverse relationship between nasal cavity and maxillary sinus volumes. Next, we examined the relationship between maxillary sinus volume and nasal cavity shape using multivariate regression. Our results show that there is a positive relationship between nasal cavity and maxillary sinus volume, indicating that the maxillary sinuses do not accommodate variation in nasal cavity size. However, maxillary sinus volume is significantly correlated with variation in relative internal nasal breadth. Thus, the maxillary sinuses appear to be important for accommodating nasal cavity shape rather than size. PMID:23382025

  7. Immediate effect of benzalkonium chloride in decongestant nasal spray on the human nasal mucosal temperature.

    PubMed

    Lindemann, J; Leiacker, R; Wiesmiller, K; Rettinger, G; Keck, T

    2004-08-01

    Benzalkonium chloride is a preservative commonly used in nasal decongestant sprays. It has been suggested that benzalkonium chloride may be harmful to the nasal mucosa. Decongestion with the vasoconstrictor xylometazoline containing benzalkonium chloride has been shown to cause a significant reduction of the nasal mucosal temperature. The purpose of the present study was to determine the short-term influence of xylometazoline nasal spray with and without benzalkonium chloride on the nasal mucosal temperature. Healthy volunteers (30) were included in the study. Fifteen volunteers received xylometazoline nasal spray (1.0 mg/mL) containing benzalkonium chloride (0.1 mg/mL) and 15 age-matched subjects, received xylometazoline nasal spray without benzalkonium chloride. Using a miniaturized thermocouple the septal mucosal temperature was continuously measured at defined intranasal detection sites before and after application of the nasal spray. The mucosal temperature values did not significantly differ between the group receiving xylometazoline containing benzalkonium chloride and the group receiving xylometazoline spray without benzalkonium chloride before and after decongestion (P > 0.05). In both study groups septal mucosal temperatures significantly decreased after decongestion (P < 0.05) because of a reduction of the nasal mucosal blood flow following vasoconstriction. This study indicates that benzalkonium chloride itself does not seem to influence nasal blood flow and nasal mucosal temperature in topical nasal decongestants. PMID:15270822

  8. Particle Image Velocimetry Measurements Inside the Human Nasal Passage

    NASA Astrophysics Data System (ADS)

    Kelly, James; Hopkins, Lisa; Sreenivas, K. R.; Wexler, Anthony; Prasad, Ajay

    1998-11-01

    In some applications (such as biological flows) the flow passage exhibits a highly complex geometry. A method is described by which such a flow passage is rendered as a three-dimensional model. A computer model of an adult human nasal cavity was generated from digitized computed tomography (CT) scan images, using the I-DEAS modeling package, and was converted to a stereolithographic file for rapid prototyping. Rapid prototyping yielded a water soluble negative of the airway. Silicone elastomer was poured over the negative, which was washed out after the silicone hardened. This technique can be used to obtain an accurate, transparent, silicone, replicate model of any arbitrary geometry. If the working fluid is refractive-index matched to the silicone, it is possible to obtain PIV measurements in any cross-section. We demonstrate the technique by creating a double-scale model of the human nasal passage, and obtaining PIV measurements.

  9. An Effective Manual Deboning Method To Prepare Intact Mouse Nasal Tissue With Preserved Anatomical Organization

    PubMed Central

    Dunston, David; Ogura, Tatsuya; Lin, Weihong

    2013-01-01

    The mammalian nose is a multi-functional organ with intricate internal structures. The nasal cavity is lined with various epithelia such as olfactory, respiratory, and squamous epithelia which differ markedly in anatomical locations, morphology, and functions. In adult mice, the nose is covered with various skull bones, limiting experimental access to internal structures, especially those in the posterior such as the main olfactory epithelium (MOE). Here we describe an effective method for obtaining almost the entire and intact nasal tissues with preserved anatomical organization. Using surgical tools under a dissecting microscope, we sequentially remove the skull bones surrounding the nasal tissue. This procedure can be performed on both paraformaldehyde-fixed and freshly dissected, skinned mouse heads. The entire deboning procedure takes about 20-30 min, which is significantly shorter than the experimental time required for conventional chemical-based decalcification. In addition, we present an easy method to remove air bubbles trapped between turbinates, which is critical for obtaining intact thin horizontal or coronal or sagittal sections from the nasal tissue preparation. Nasal tissue prepared using our method can be used for whole mount observation of the entire epithelia, as well as morphological, immunocytochemical, RNA in situ hybridization, and physiological studies, especially in studies where region-specific examination and comparison are of interest. PMID:23963491

  10. Treatment of nasal hemangiomas.

    PubMed

    Simic, R; Vlahovic, A; Subarevic, V

    2009-10-01

    Hemangiomas are the most common soft tissue tumors of infancy. Almost 60% of these tumors develop in the head and neck region. Nasal hemangiomas, distort human physiognomy and leave long lasting psychological sequelae. Conservative approach (intralesional corticosteroids, laser) may accelerate involution. Proponents of an early surgery suggest that aesthetic improvement during a critical period in child development can be achieved. Fourteen patients with nasal hemangioma were treated during 5-year period (2003-2007) with intralesional corticosteroids, lenticular excision, open rhinoplasty excision, and circular excision with "purse string suture". The first line of treatment for large nasal hemangiomas is intralesional corticosteroids. Excision is indicated for small hemangiomas, while subtotal excision is preferable for large nasal hemangiomas. Circular excision and "purse string suture" is appropriate for prominent hemangiomas with predominant deep component. In our opinion surgery with maximal care for nasal architecture is the treatment option for nasal hemangioma. PMID:19656579

  11. Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption.

    PubMed

    Al-Ghabeish, Manar; Scheetz, Todd; Assem, Mahfoud; Donovan, Maureen D

    2015-08-01

    Mice and rats are commonly used to investigate in vivo nasal drug absorption, yet their small nasal cavities limit their use for in vitro investigations. Bovine tissue explants have been used to investigate drug transport through the nasal respiratory and olfactory mucosae, yet limited information is available regarding the similarities and differences among these animal models compared to humans. The aim of this study was to compare the presence of a number of important drug transporters in the nasal mucosa of these species. DNA microarray results for nasal samples from humans, rats, and mice were obtained from GenBank, while DNA microarray and RT-PCR were performed on bovine nasal explants. The drug transporters of interest include multidrug resistance, cation, anion, peptide, and nucleoside transporters. Each of the species (mouse, rat, cattle, and human) shows similar patterns of expression for most of the important drug transporters. Several transporters were highly expressed in all the species, including MRP1, OCTN2, PEPT2, and y+LAT2. While some differences in transporter mRNA and protein expression were observed, the transporter expression patterns were quite similar among the species. The differences suggest that it is important to be aware of any specific differences in transporter expression for a given compound being investigated, yet the similarities support the continued use of these animal models during preclinical investigation of intranasally administered therapeutics. PMID:26106909

  12. Microarray Determination of the Expression of Drug Transporters in Humans and Animal Species Used for the Investigation of Nasal Absorption

    PubMed Central

    Al-Ghabeish, Manar; Scheetz, Todd; Assem, Mahfoud; Donovan, Maureen D.

    2015-01-01

    Purpose Mice and rats are commonly used to investigate in vivo nasal drug absorption, yet their small nasal cavities limit their use for in vitro investigations. Bovine tissue explants have been used to investigate drug transport through the nasal respiratory and olfactory mucosae, yet limited information is available regarding the similarities and differences among these animal models compared to humans. The aim of this study was to compare the presence of a number of important drug transporters in the nasal mucosa of these species. Methods DNA microarray results for nasal samples from humans, rats and mice were obtained from GenBank, while DNA microarray and RT-PCR were performed on bovine nasal explants. The drug transporters of interest include multidrug resistance, cation, anion, peptide, and nucleoside transporters. Results Each of the species (mouse, rat, cow and human) shows similar patterns of expression for most of the important drug transporters. Several transporters were highly expressed in all the species, including MRP1, OCTN2, PEPT2 and y+LAT2. Conclusion While some differences in transporter mRNA and protein expression were observed, the transporter expression patterns were quite similar among the species. The differences suggest that it is important to be aware of any specific differences in transporter expression for a given compound being investigated, yet the similarities support the continued use of these animal models during preclinical investigation of intranasally administered therapeutics. PMID:26106909

  13. Impact Assessment of Repeated Exposure of Organotypic 3D Bronchial and Nasal Tissue Culture Models to Whole Cigarette Smoke

    PubMed Central

    Kuehn, Diana; Majeed, Shoaib; Guedj, Emmanuel; Dulize, Remi; Baumer, Karine; Iskandar, Anita; Boue, Stephanie; Martin, Florian; Kostadinova, Radina; Mathis, Carole; Ivanov, Nikolai V.; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C.

    2015-01-01

    Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease or lung cancer. To understand the underlying mechanisms of disease development, it would be important to examine the impact of CS exposure directly on lung tissues. However, this approach is difficult to implement in epidemiological studies because lung tissue sampling is complex and invasive. Alternatively, tissue culture models can facilitate the assessment of exposure impacts on the lung tissue. Submerged 2D cell cultures, such as normal human bronchial epithelial (NHBE) cell cultures, have traditionally been used for this purpose. However, they cannot be exposed directly to smoke in a similar manner to the in vivo exposure situation. Recently developed 3D tissue culture models better reflect the in vivo situation because they can be cultured at the air-liquid interface (ALI). Their basal sides are immersed in the culture medium; whereas, their apical sides are exposed to air. Moreover, organotypic tissue cultures that contain different type of cells, better represent the physiology of the tissue in vivo. In this work, the utilization of an in vitro exposure system to expose human organotypic bronchial and nasal tissue models to mainstream CS is demonstrated. Ciliary beating frequency and the activity of cytochrome P450s (CYP) 1A1/1B1 were measured to assess functional impacts of CS on the tissues. Furthermore, to examine CS-induced alterations at the molecular level, gene expression profiles were generated from the tissues following exposure. A slight increase in CYP1A1/1B1 activity was observed in CS-exposed tissues compared with air-exposed tissues. A network-and transcriptomics-based systems biology approach was sufficiently robust to demonstrate CS-induced alterations of xenobiotic metabolism that were similar to those observed in the bronchial and nasal epithelial cells obtained from smokers. PMID:25741927

  14. Impact assessment of repeated exposure of organotypic 3D bronchial and nasal tissue culture models to whole cigarette smoke.

    PubMed

    Kuehn, Diana; Majeed, Shoaib; Guedj, Emmanuel; Dulize, Remi; Baumer, Karine; Iskandar, Anita; Boue, Stephanie; Martin, Florian; Kostadinova, Radina; Mathis, Carole; Ivanov, Nikolai V; Frentzel, Stefan; Hoeng, Julia; Peitsch, Manuel C

    2015-01-01

    Cigarette smoke (CS) has a major impact on lung biology and may result in the development of lung diseases such as chronic obstructive pulmonary disease or lung cancer. To understand the underlying mechanisms of disease development, it would be important to examine the impact of CS exposure directly on lung tissues. However, this approach is difficult to implement in epidemiological studies because lung tissue sampling is complex and invasive. Alternatively, tissue culture models can facilitate the assessment of exposure impacts on the lung tissue. Submerged 2D cell cultures, such as normal human bronchial epithelial (NHBE) cell cultures, have traditionally been used for this purpose. However, they cannot be exposed directly to smoke in a similar manner to the in vivo exposure situation. Recently developed 3D tissue culture models better reflect the in vivo situation because they can be cultured at the air-liquid interface (ALI). Their basal sides are immersed in the culture medium; whereas, their apical sides are exposed to air. Moreover, organotypic tissue cultures that contain different type of cells, better represent the physiology of the tissue in vivo. In this work, the utilization of an in vitro exposure system to expose human organotypic bronchial and nasal tissue models to mainstream CS is demonstrated. Ciliary beating frequency and the activity of cytochrome P450s (CYP) 1A1/1B1 were measured to assess functional impacts of CS on the tissues. Furthermore, to examine CS-induced alterations at the molecular level, gene expression profiles were generated from the tissues following exposure. A slight increase in CYP1A1/1B1 activity was observed in CS-exposed tissues compared with air-exposed tissues. A network-and transcriptomics-based systems biology approach was sufficiently robust to demonstrate CS-induced alterations of xenobiotic metabolism that were similar to those observed in the bronchial and nasal epithelial cells obtained from smokers. PMID:25741927

  15. Nasal Associated Lymphoid Tissue of the Syrian Golden Hamster Expresses High Levels of PrPC

    PubMed Central

    Clouse, Melissa D.; Shikiya, Ronald A.; Bartz, Jason C.; Kincaid, Anthony E.

    2015-01-01

    The key event in the pathogenesis of the transmissible spongiform encephalopathies is a template-dependent misfolding event where an infectious isoform of the prion protein (PrPSc) comes into contact with native prion protein (PrPC) and changes its conformation to PrPSc. In many extraneurally inoculated models of prion disease this PrPC misfolding event occurs in lymphoid tissues prior to neuroinvasion. The primary objective of this study was to compare levels of total PrPC in hamster lymphoid tissues involved in the early pathogenesis of prion disease. Lymphoid tissues were collected from golden Syrian hamsters and Western blot analysis was performed to quantify PrPC levels. PrPC immunohistochemistry (IHC) of paraffin embedded tissue sections was performed to identify PrPC distribution in tissues of the lymphoreticular system. Nasal associated lymphoid tissue contained the highest amount of total PrPC followed by Peyer’s patches, mesenteric and submandibular lymph nodes, and spleen. The relative levels of PrPC expression in IHC processed tissue correlated strongly with the Western blot data, with high levels of PrPC corresponding with a higher percentage of PrPC positive B cell follicles. High levels of PrPC in lymphoid tissues closely associated with the nasal cavity could contribute to the relative increased efficiency of the nasal route of entry of prions, compared to other routes of infection. PMID:25642714

  16. Reduced Expression of Antimicrobial PLUNC Proteins in Nasal Polyp Tissues of patients with Chronic Rhinosinusitis

    PubMed Central

    Seshadri, Sudarshan; Lin, David C.; Rosati, Mariel; Carter, Roderick G.; Norton, James E.; Suh, Lydia; Kato, Atsushi; Chandra, Rakesh K.; Harris, Kathleen E.; Chu, Hong Wei; Peters, Anju T.; Tan, Bruce K.; Conley, David B.; Grammer, Leslie C.; Kern, Robert C.; Schleimer, Robert P.

    2012-01-01

    Background Chronic rhinosinusitis (CRS) is a disease characterized by inflammation of the nasal mucosa and paranasal sinuses. This inflammation may result in part from decreased epithelial barrier and innate immune responses, leading to frequent bacterial and fungal colonization. The objectives of this study were to investigate the expression of innate immune proteins of the Palate Lung and Nasal epithelium Clone (PLUNC) family in patients with CRS. Methods Nasal tissue samples were collected from control subjects and CRS patients with and without nasal polyps. Expression of the members of the PLUNC family was analyzed by real-time PCR. Expression of SPLUNC1 and LPLUNC2 proteins was analyzed by ELISA, immunoblot and immunohistochemical analysis. Results Levels of mRNA for most of the members of the PLUNC family were profoundly reduced in nasal polyps (NPs) compared to uncinate tissue from control subjects or CRS patients. LPLUNC2 and SPLUNC1 proteins were decreased in NPs of CRS patients compared to uncinate tissue from control subjects. Immunohistochemical data revealed that within submucosal glands of sinonasal tissues, SPLUNC1 and LPLUNC2 were differentially expressed, in serous and mucous cells, respectively. The decrease in expression of these molecules is probably explained by a decrease in the number of glands in NPs as revealed by correlations with levels of the glandular marker lactoferrin. Conclusions Decreased SPLUNC1 and LPLUNC2 in NPs reflects a profound decrease in the number of submucosal glands. Decreased glands may lead to a localized defect in the production and release of glandular innate defense molecules. PMID:22676062

  17. Human umbilical cord mesenchymal stem cells alleviate nasal mucosa radiation damage in a guinea pig model.

    PubMed

    Duan, Hong-Gang; Ji, Fang; Zheng, Chun-Quan; Wang, Chun-Hua; Li, Jing

    2015-02-01

    Nasal complications after radiotherapy severely affect the quality of life of nasopharyngeal carcinoma patients, and there is a compelling need to find novel therapies for nasal epithelial cell radiation damage. Therefore, we investigated the therapeutic effect of human umbilical cord mesenchymal stem cells (hUC-MSCs) in guinea pig model of nasal mucosa radiation damage and explored its therapeutic mechanism. Cultured hUC-MSCs were injected intravenously immediately after radiation in the nasal mucosa-radiation-damage guinea pig model. Migration of hUC-MSCs into the nasal mucosa and the potential for differentiation into nasal epithelial cells were evaluated by immunofluorescence. The therapeutic effects of hUC-MSCs were evaluated by mucus clearance time (MCT), degree of nasal mucosa edema, and the nasal mucosa cilia form and coverage ratio. Results indicate that the hUC-MSCs migrated to the nasal mucosa lamina propria and did not differentiate into nasal epithelial cells in this model. The MCT and degree of mucosal edema were improved at 1 week and 1 month after radiation, respectively, but no difference was found at 3 months and 6 months after radiation. The nasal mucosa cilia form and coverage ratio was not improved 6 months after radiation. Thus, hUC-MSCs can migrate to the nasal mucosa lamina propria and improve MCT and mucosa edema within a short time period, but these cells are unable to differentiate into nasal epithelial cells and improve nasal epithelial regeneration in the nasal mucosa radiation damage guinea pig model. PMID:25209829

  18. Targeted delivery of antigen to hamster nasal lymphoid tissue with M-cell-directed lectins.

    PubMed Central

    Giannasca, P J; Boden, J A; Monath, T P

    1997-01-01

    The nasal cavity of a rodent is lined by an epithelium organized into distinct regional domains responsible for specific physiological functions. Aggregates of nasal lymphoid tissue (NALT) located at the base of the nasal cavity are believed to be sites of induction of mucosal immune responses to airborne antigens. The epithelium overlying NALT contains M cells which are specialized for the transcytosis of immunogens, as demonstrated in other mucosal tissues. We hypothesized that NALT M cells are characterized by distinct glycoconjugate receptors which influence antigen uptake and immune responses to transcytosed antigens. To identify glycoconjugates that may distinguish NALT M cells from other cells of the respiratory epithelium (RE), we performed lectin histochemistry on sections of the hamster nasal cavity with a panel of lectins. Many classes of glycoconjugates were found on epithelial cells in this region. While most lectins bound to sites on both the RE and M cells, probes capable of recognizing alpha-linked galactose were found to label the follicle-associated epithelium (FAE) almost exclusively. By morphological criteria, the FAE contains >90% M cells. To determine if apical glycoconjugates on M cells were accessible from the nasal cavity, an M-cell-selective lectin and a control lectin in parallel were administered intranasally to hamsters. The M-cell-selective lectin was found to specifically target the FAE, while the control lectin did not. Lectin bound to M cells in vivo was efficiently endocytosed, consistent with the role of M cells in antigen transport. Intranasal immunization with lectin-test antigen conjugates without adjuvant stimulated induction of specific serum immunoglobulin G, whereas antigen alone or admixed with lectin did not. The selective recognition of NALT M cells by a lectin in vivo provides a model for microbial adhesin-host cell receptor interactions on M cells and the targeted delivery of immunogens to NALT following intranasal

  19. Human nasal rhinosporidiosis: a case report from Malawi

    PubMed Central

    Uledi, Sefu; Fauzia, Ayubu

    2011-01-01

    Rhinosporidiosis is a rare chronic granulomatous disease, characterised by polypous lesions of the mucous membrane. Commonly affects the mucous membrane of the naso-pharynx, conjunctiva and palate. Its causative agent is Rhinosporidium seeberi. The disease is more prevalent in the Indian subcontinent, but remains quite rare in our environment. We hereby present a case description of a 70 year old native Malawian male with a polypoid nasal rhinosporidiosis. Patient presented with long standing history of nasal obstruction and intermittent epistaxis for three years. Diagnosis was confirmed by histopathological examination and he was successfully treated by complete surgical excision. This was a very unusual cause of nasal masses in our setting. Nasal rhinosporidioss lesions may largely mimic other ordinary nasal polyps, it is crucial therefore for clinicians in our region to consider rhinosporidiosis as a differential diagnosis when assessing patients presenting with nasal swellings. PMID:22355433

  20. Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion.

    PubMed

    Bas, Esperanza; Van De Water, Thomas R; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M; Goldstein, Bradley J

    2014-03-01

    A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

  1. Primary human nasal epithelial cell response to titanium surface with a nanonetwork structure in nasal implant applications

    NASA Astrophysics Data System (ADS)

    Yang, Wei-En; Lan, Ming-Ying; Lee, Sheng-Wei; Chang, Jeng-Kuei; Huang, Her-Hsiung

    2015-04-01

    In nasal reconstruction applications, the response of cells to titanium (Ti) implants is largely determined by the surface characteristics of the implant. This study investigated an electrochemical anodization surface treatment intended to improve the response of primary human nasal epithelial cells (HNEpC) to Ti surfaces in nasal implant applications. We used a simple and fast electrochemical anodization treatment, i.e., applying anodic current, to produce a titanium dioxide (TiO2) nanonetwork layer on the Ti surface with average lateral pore size below 100 nm, depending on the current applied. The TiO2 nanonetwork layer exhibited enhanced hydrophilicity and protein adsorption ability compared with untreated Ti surfaces. In addition, the spreading morphology, cytoskeletal arrangement, and proliferation of HNEpC on the nanonetwork layer indicated excellent cell response characteristics. This research advances our understanding regarding the means by which a TiO2 nanonetwork layer can improve the response of HNEpC to Ti surfaces in nasal implant applications.

  2. Resident aerobic microbiota of the adult human nasal cavity.

    PubMed

    Rasmussen, T T; Kirkeby, L P; Poulsen, K; Reinholdt, J; Kilian, M

    2000-10-01

    Recent evidence strongly suggests that the microbiota of the nasal cavity plays a crucial role in determining the reaction patterns of the mucosal and systemic immune system. However, little is known about the normal microbiota of the nasal cavity. The purpose of this study was to determine the microbiota in different parts of the nasal cavity and to develop and evaluate methods for this purpose. Samples were collected from 10 healthy adults by nasal washes and by swabbing of the mucosa through a sterile introduction device. Both methods gave results that were quantitatively and qualitatively reproducible, and revealed significant differences in the density of the nasal microbiota between individuals. The study revealed absence of gram-negative bacteria that are regular members of the commensal microbiota of the pharynx. Likewise, viridans type streptococci were sparsely represented. The nasal microbiota was dominated by species of the genera Corynebacterium, Aureobacterium, Rhodococcus, and Staphylococcus, including S. epidermis, S. capitis, S. hominis, S. haemolyticus, S. lugdunensis and S. warneri. These studies show that the microbiota of the nasal cavity of adults is strikingly different from that of the pharynx, and that the nasal cavity is a primary habitat for several species of diphtheroids recognized as opportunistic pathogens. Under special circumstances, single species, including IgA1 protease-producing bacteria, may become predominant in a restricted area of the nasal mucosa. PMID:11200821

  3. In vivo deposition of ultrafine aerosols in human nasal and oral airways

    SciTech Connect

    Yeh, Hsu-Chi; Swift, D.L.; Simpson, S.Q.

    1995-12-01

    The extrathoracic airways, including the nasal passage, oral passage, pharynx, and larynx, are the first targets for inhaled particles and provide an important defense for the lung. Understanding the deposition efficiency of the nasal and oral passages is therefore crucial for assessing doses of inhaled particles to the extrathoracic airways and the lung. Significant inter-subject variability in nasal deposition has been shown in recent studies by Rasmussen, T.R. et al, using 2.6 {mu}m particles in 10 human subjects and in our preliminary studies using 0.004-0.15 {mu}m particles in four adult volunteers. No oral deposition was reported in either of these studies. Reasons for the intersubject variations have been frequently attributed to the geometry of the nasal passages. The aims of the present study were to measure in vivo the nasal airway dimensions and the deposition of ultrafine aerosols in both the nasal and oral passages, and to determine the relationship between nasal airway dimensions and aerosol deposition. A statistical procedure incorporated with the diffusion theory was used to model the dimensional features of the nasal airways which may be responsible for the biological variability in particle deposition. In summary, we have correlated deposition of particles in the size range of 0.004 to 0.15 {mu}m with the nasal dimensions of each subject.

  4. A Review of the Comparative Anatomy, Histology, Physiology and Pathology of the Nasal Cavity of Rats, Mice, Dogs and Non-human Primates. Relevance to Inhalation Toxicology and Human Health Risk Assessment.

    PubMed

    Chamanza, R; Wright, J A

    2015-11-01

    There are many significant differences in the structural and functional anatomy of the nasal cavity of man and laboratory animals. Some of the differences may be responsible for the species-specific nasal lesions that are often observed in response to inhaled toxicants. This paper reviews the comparative anatomy, physiology and pathology of the nasal cavity of the rat, mouse, dog, monkey and man, highlighting factors that may influence the distribution of nasal lesions. Gross anatomical variations such as turbinate structure, folds or grooves on nasal walls, or presence or absence of accessory structures, may influence nasal airflow and species-specific uptake and deposition of inhaled material. In addition, interspecies variations in the morphological and biochemical composition and distribution of the nasal epithelium may affect the local tissue susceptibility and play a role in the development of species-specific nasal lesions. It is concluded that, while the nasal cavity of the monkey might be more similar to that of man, each laboratory animal species provides a model that responds in a characteristic and species-specific manner. Therefore for human risk assessment, careful consideration must be given to the anatomical differences between a given animal model and man. PMID:26460093

  5. COMMENTS ON RECENT DATA FOR PARTICLE DEPOSITION IN HUMAN NASAL PASSAGES

    EPA Science Inventory

    The deposition of inhaled particles within human nasal passages has important toxicologic and pharmacologic applications. owever, experimental data quantitating factors affecting particle deposition are rare. e have evaluated findings from investigations employing either replica ...

  6. MORPHOMETRIC ASPECTS OF CILIARY DISTRIBUTION AND CILIOGENESIS IN HUMAN NASAL EPITHELIUM

    EPA Science Inventory

    Observations of freeze-fracture preparations of human nasal epithelium have provided a unique perspective of the spatial distribution of epithelial cell cilia unattainable by more conventional ultrastructural techniques. The initial stages of ciliogenesis were characterized ultra...

  7. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.

    PubMed

    Guastella, Adam J; Hickie, Ian B; McGuinness, Margaret M; Otis, Melissa; Woods, Elizabeth A; Disinger, Hannah M; Chan, Hak-Kim; Chen, Timothy F; Banati, Richard B

    2013-05-01

    A series of studies have reported on the salubrious effects of oxytocin nasal spray on social cognition and behavior in humans, across physiology (e.g., eye gaze, heart rate variability), social cognition (e.g., attention, memory, and appraisal), and behavior (e.g., trust, generosity). Findings suggest the potential of oxytocin nasal spray as a treatment for various psychopathologies, including autism and schizophrenia. There are, however, increasing reports of variability of response to oxytocin nasal spray between experiments and individuals. In this review, we provide a summary of factors that influence transmucosal nasal drug delivery, deposition, and their impact on bioavailability. These include variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation (including presence of uptake enhancers, control release formulation), and amount and method of administration. These key variables are generally poorly described and controlled in scientific reports, in spite of their potential to alter the course of treatment outcome studies. Based on this review, it should be of no surprise that differences emerge across individuals and experiments when nasal drug delivery methods are employed. We present recommendations for researchers to use when developing and administering the spray, and guidelines for reporting on peptide nasal spray studies in humans. We hope that these recommendations assist in establishing a scientific standard that can improve the rigor and subsequent reliability of reported effects of oxytocin nasal spray in humans. PMID:23265311

  8. Expression of P-glycoprotein in excised human nasal mucosa and optimized models of RPMI 2650 cells.

    PubMed

    Dolberg, Anne M; Reichl, Stephan

    2016-07-11

    To assess the transmucosal drug transport in the development of medications for intranasal administration, cellular in vitro models are preferred over the use of animal tissues due to inter-species variations and ethical concerns. With regard to the distribution of active agents and multidrug resistance, the ABC transporter P-glycoprotein plays a major role in several mammalian tissues. The present study compares the expression of this efflux pump in optimized in vitro models based on the human RPMI 2650 cell line with specimens of human turbinate mucosa. The presence of the ABCB1 gene was investigated at the mRNA and protein levels using RT-PCR and Western blot analysis in differently cultured RPMI 2650 cells and excised human nasal epithelium. Furthermore, the localization and activity of P-gp was examined by immunohistochemical staining and functionality assays using different substrates in both in vitro and ex vivo models. Both mRNA and protein expression of P-gp was found in all studied models. Furthermore, transporter functionality was detected in both RPMI 2650 cell culture models and excised human mucosa. The results demonstrated a highly promising comparability between RPMI 2650 models and explants of human nasal tissue concerning the influence of MDR1 on drug disposition. The RPMI 2650 cell line might become a useful tool in preclinical trials to improve reproducibility and achieve greater applicability to humans of experimental data regarding passive diffusion and active efflux of drug candidates. PMID:27155589

  9. Inhalation of nasally derived nitric oxide modulates pulmonary function in humans.

    PubMed

    Lundberg, J O; Settergren, G; Gelinder, S; Lundberg, J M; Alving, K; Weitzberg, E

    1996-12-01

    The vasodilator gas nitric oxide (NO) is produced in the paranasal sinuses and is excreted continuously into the nasal airways of humans. This NO will normally reach the lungs with inspiration, especially during nasal breathing. We wanted to investigate the possible effects of low-dose inhalation of NO from the nasal airways on pulmonary function. The effects of nasal and oral breathing on transcutaneous oxygen tension (tcPO2) were studied in healthy subjects. Furthermore, we also investigated whether restoring low-dose NO inhalation would influence pulmonary vascular resistance index (PVRI) and arterial oxygenation (PaO2) in intubated patients who are deprived of NO produced in the nasal airways. Thus, air derived from the patient's own nose was aspirated and led into the inhalation limb of the ventilator. In six out of eight healthy subjects tcPO2 was 10% higher during periods of nasal breathing when compared with periods of oral breathing. In six out of six long-term intubated patients PaO2 increased by 18% in response to the addition of nasal air samples. PVRI was reduced by 11% in four of 12 short-term intubated patients when nasal air was added to the inhaled air. The present study demonstrates that tcPO2 increases during nasal breathing compared with oral breathing in healthy subjects. Furthermore, in intubated patients, who are deprived of self-inhalation of endogenous NO. PaO2 increases and pulmonary vascular resistance may decrease by adding NO-containing air, derived from the patient's own nose, to the inspired air. The involvement of self-inhaled NO in the regulation of pulmonary function may represent a novel physiological principle, namely that of an enzymatically produced airborne messenger. Furthermore, our findings may help to explain one biological role of the human paranasal sinuses. PMID:8971255

  10. Nasal vascularization: experiences using the microcorrosion technique in human foetuses.

    PubMed

    Passàli, D; Buccella, M G; Vetuschi, A; Bellussi, L

    1992-06-01

    The authors have studied the three-dimensional aspect of the vascular architecture of the nasal mucosa, using the microcorrosion method followed by scanning electron microscopical observation of casts of the vascular networks in both the septum and the lateral part of the nose. Batson's compound was introduced into the vascular system through the ascending aorta, in order to obtain a replica of the nasal mucosa vessels. Twelve- to 24-week-old foetuses obtained from spontaneous abortions were used for this purpose. PMID:1411101

  11. Kinetics of naphthalene metabolism in target and non-target tissues of rodents and in nasal and airway microsomes from the Rhesus monkey

    SciTech Connect

    Buckpitt, Alan; Morin, Dexter; Murphy, Shannon; Edwards, Patricia; Van Winkle, Laura

    2013-07-15

    Naphthalene produces species and cell selective injury to respiratory tract epithelial cells of rodents. In these studies we determined the apparent K{sub m}, V{sub max}, and catalytic efficiency (V{sub max}/K{sub m}) for naphthalene metabolism in microsomal preparations from subcompartments of the respiratory tract of rodents and non-human primates. In tissues with high substrate turnover, major metabolites were derived directly from naphthalene oxide with smaller amounts from conjugates of diol epoxide, diepoxide, and 1,2- and 1,4-naphthoquinones. In some tissues, different enzymes with dissimilar K{sub m} and V{sub max} appeared to metabolize naphthalene. The rank order of V{sub max} (rat olfactory epithelium > mouse olfactory epithelium > murine airways ≫ rat airways) correlated well with tissue susceptibility to naphthalene. The V{sub max} in monkey alveolar subcompartment was 2% that in rat nasal olfactory epithelium. Rates of metabolism in nasal compartments of the monkey were low. The catalytic efficiencies of microsomes from known susceptible tissues/subcompartments are 10 and 250 fold higher than in rat airway and monkey alveolar subcompartments, respectively. Although the strong correlations between catalytic efficiencies and tissue susceptibility suggest that non-human primate tissues are unlikely to generate metabolites at a rate sufficient to produce cellular injury, other studies showing high levels of formation of protein adducts support the need for additional studies. - Highlights: • Naphthalene is metabolized with high catalytic efficiency in susceptible tissue. • Naphthalene is metabolized at low catalytic efficiency in non-susceptible tissue. • Respiratory tissues of the non human primate metabolize naphthalene slowly.

  12. Nasal Anatomy

    MedlinePlus

    ... Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure Statement CONDITIONS Adult ... Nasal Anatomy Sinus Anatomy Nasal Physiology Nasal Endoscopy Skull Base Anatomy Virtual Anatomy Disclosure Statement Printer Friendly ...

  13. Nasal mucosal biopsy

    MedlinePlus

    Biopsy - nasal mucosa; Nose biopsy ... to fast for a few hours before the biopsy. ... Nasal mucosal biopsy is usually done when abnormal tissue is seen during examination of the nose. It may also be done ...

  14. Human Reconstituted Nasal Epithelium, a promising in vitro model to assess impacts of environmental complex mixtures.

    PubMed

    Bardet, Gaëlle; Mignon, Virginie; Momas, Isabelle; Achard, Sophie; Seta, Nathalie

    2016-04-01

    Considering the impact of respiratory diseases around the world, appropriate experimental tools to help understand the mechanisms involved in such diseases are becoming essential. Our aim was to investigate the cellular and morphological reactivity of a human Reconstituted Nasal Epithelium (hRNE) to evaluate the impact of environmental complex mixture (ECM), with tobacco smoke as a model, after three weeks of repeated exposures. Staining of hRNE showed a multilayered ciliated epithelium, with a regular cilia beats, and a mucus production. When hRNE was exposed to ECM for 5 min once or twice a week, during 3 weeks, significant changes occurred: IL-8 production significantly increased 24h after the first exposure compared with Air-exposure and only during the first week, without any loss of tissue integrity. Immunostaining of F-actin cytoskeleton showed a modification in cellular morphology (number and diameter). Taken together our results indicate that hRNE is well suited to study the cellular and morphological effects of repeated exposures to an environmental complex mixture. Human reconstituted epithelium models are currently the best in vitro representation of human respiratory tract physiology, and also the most robust for performing repeated exposures to atmospheric pollutants. PMID:26631767

  15. Induction by inhibitors of nitric oxide synthase of hyperresponsiveness in the human nasal airway

    PubMed Central

    Turner, P J; Maggs, J R L; Foreman, J C

    2000-01-01

    The effects of inhibitors of nitric oxide synthase (NOS) on the responsiveness of the human nasal airway were investigated, by measuring the nasal response to histamine and bradykinin. Repeated intranasal administration of NG-nitro-L-arginine methyl ester (L-NAME) or NG-monomethyl-L-arginine (L-NMMA), 1 μmol per nostril every 30 min for 6 h, increased the nasal obstruction induced by histamine, 50–500 μg, and bradykinin, 200 μg per nostril. A single administration of L-NAME, 1 μmol per nostril did not induce hyperresponsiveness to histamine. Pretreatment with L-arginine, 30 μmol, abolished the hyperresponsiveness to histamine caused by L-NAME, 1 μmol. Pretreatment with NG-nitro-D-arginine methyl ester (D-NAME), 1 μmol, did not induce hyperresponsiveness to histamine. Repeated administration of L-NAME, 1 μmol, caused a significant reduction in the amount of nitric oxide measured in the nasal cavity. Neither L-NMMA, 1 μmol, nor L-arginine, 30 μmol, altered the nasal hyperresponsiveness induced by platelet activating factor (PAF), 60 μg. PAF did not alter the levels of nitric oxide in the nasal cavity. The results suggest that inhibition of nitric oxide synthase induces a hyperresponsiveness in the human nasal airway, and that this occurs by a mechanism different from that involved in PAF-induced hyperresponsiveness. PMID:10991932

  16. Neutrophil influx measured in nasal lavages of humans exposed to ozone

    SciTech Connect

    Graham, D.; Henderson, F.; House, D.

    1988-05-01

    Neutrophils (PMNs) obtained by nasal lavage were counted to determine if ozone, an oxidant air pollutant, induces an acute inflammatory response in the upper respiratory tract (URT) of humans. Background data were obtained by the nasal lavages from 200 nonexperimentally exposed subjects. Then, using a known inflammatory agent for the URT, rhinovirus-type 39, the induction, peak, and resolution of an acute inflammatory response was shown to be documented by the nasal lavage PMN counts. To determined if ozone induces this response, 41 subjects were exposed to either filtered air or 0.5 ppm ozone for 4 hr, on 2 consecutive days. Nasal lavages were taken pre-, immediately post each exposure, and 22 hr following the last exposure. Lavage PMN counts increased significantly (p = .005) in the ozone-exposed group, with 3.5-, 6.5-, and 3.9-fold increases over the air-exposed group at the post 1, pre 2, and post 2 time points, respectively. Ozone induces an inflammatory response in the URT of humans, and nasal lavage PMN counts are useful to assay the inflammatory properties of air pollutants.

  17. Aspects of nitrogen dioxide toxicity in environmental urban concentrations in human nasal epithelium

    SciTech Connect

    Koehler, C.; Ginzkey, C.; Friehs, G.; Hackenberg, S.; Froelich, K.; Scherzed, A.; Burghartz, M.; Kessler, M.; Kleinsasser, N.

    2010-06-01

    Cytotoxicity and genotoxicity of nitrogen dioxide (NO{sub 2}) as part of urban exhaust pollution are widely discussed as potential hazards to human health. This study focuses on toxic effects of NO{sub 2} in realistic environmental concentrations with respect to the current limit values in a human target tissue of volatile xenobiotics, the epithelium of the upper aerodigestive tract. Nasal epithelial cells of 10 patients were cultured as an air-liquid interface and exposed to 0.01 ppm NO{sub 2}, 0.1 ppm NO{sub 2}, 1 ppm NO{sub 2}, 10 ppm NO{sub 2} and synthetic air for half an hour. After exposure, genotoxicity was evaluated by the alkaline single-cell microgel electophoresis (Comet) assay and by induction of micronuclei in the micronucleus test. Depression of proliferation and cytotoxic effects were determined using the micronucleus assay and trypan blue exclusion assay, respectively. The experiments revealed genotoxic effects by DNA fragmentation starting at 0.01 ppm NO{sub 2} in the Comet assay, but no micronucleus inductions, no changes in proliferation, no signs of necrosis or apoptosis in the micronucleus assay, nor did the trypan blue exclusion assay show any changes in viability. The present data reveal a possible genotoxicity of NO{sub 2} in urban concentrations in a screening test. However, permanent DNA damage as indicated by the induction of micronuclei was not observed. Further research should elucidate the effects of prolonged exposure.

  18. From the Cover: Comparative Numerical Modeling of Inhaled Nanoparticle Deposition in Human and Rat Nasal Cavities.

    PubMed

    Dong, Jingliang; Shang, Yidan; Inthavong, Kiao; Tu, Jiyuan; Chen, Rui; Bai, Ru; Wang, Dongliang; Chen, Chunying

    2016-08-01

    To gain a better understanding of nanoparticle exposure in human nasal cavities, laboratory animals (e.g. rat) are used for in vivo studies. However, due to anatomical differences between human and rodent nasal cavities, direct particle deposition comparisons between species are difficult. This paper presents a comparative nanoparticle (1 nm, 10 nm, and 100 nm) deposition study using anatomically realistic models of a human and rat nasal cavity. The particle deposition fraction was highest consistently in the main nasal passage, for all nanoparticles tested, in the human model; whereas this was only the case for 10 nm, and 100 nm particles for the rodent model, where greater deposition was found in the anterior nose for 1 nm particles. A deposition intensity (DI) term was introduced to represent the accumulated deposition fraction on cross-sectional slices. A common and preferential deposition site in the human model was found for all nanoparticles occurring at a distance of 3.5 cm inside the nasal passage. For the rodent model maximum DI occurred in the vestibule region at a distance of 0.3 cm, indicating that the rodent vestibule produces exceptionally high particle filtration capability. We also introduced a deposition flux which was a ratio of the regional deposition fraction relative to the region's surface area fraction. This value allowed direct comparison of deposition flux between species, and a regional extrapolation scaling factor was found (e.g. 1/10 scale for vestibule region for rat to human comparison). This study bridges the in vitro exposure experiments and in vivo nanomaterials toxicity studies, and can contribute towards improving inter-species exposure extrapolation studies in the future. PMID:27208081

  19. Human Tissue Stimulator

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Neurodyne Corporation Human Tissue Stimulator (HTS) is a totally implantable system used for treatment of chronic pain and involuntary motion disorders by electrical stimulation. It was developed by Pacesetter Systems, Inc. in cooperation with the Applied Physics Laboratory. HTS incorporates a nickel cadmium battery, telemetry and command systems technologies of the same type as those used in NASA's Small Astronomy Satellite-3 in microminiature proportions so that the implantable element is the size of a deck of cards. The stimulator includes a rechargeable battery, an antenna and electronics to receive and process commands and to report on its own condition via telemetry, a wireless process wherein instrument data is converted to electrical signals and sent to a receiver where signals are presented as usable information. The HTS is targeted to nerve centers or to particular areas of the brain to provide relief from intractable pain or arrest involuntary motion. The nickel cadmium battery can be recharged through the skin. The first two HTS units were implanted last year and have been successful. Extensive testing is required before HTS can be made available for general use.

  20. Polyvinylidene fluoride film based nasal sensor to monitor human respiration pattern: an initial clinical study.

    PubMed

    Roopa Manjunatha, G; Rajanna, K; Mahapatra, D Roy; Nayak, M M; Krishnaswamy, Uma Maheswari; Srinivasa, R

    2013-12-01

    Design and development of a piezoelectric polyvinylidene fluoride (PVDF) thin film based nasal sensor to monitor human respiration pattern (RP) from each nostril simultaneously is presented in this paper. Thin film based PVDF nasal sensor is designed in a cantilever beam configuration. Two cantilevers are mounted on a spectacle frame in such a way that the air flow from each nostril impinges on this sensor causing bending of the cantilever beams. Voltage signal produced due to air flow induced dynamic piezoelectric effect produce a respective RP. A group of 23 healthy awake human subjects are studied. The RP in terms of respiratory rate (RR) and Respiratory air-flow changes/alterations obtained from the developed PVDF nasal sensor are compared with RP obtained from respiratory inductance plethysmograph (RIP) device. The mean RR of the developed nasal sensor (19.65 ± 4.1) and the RIP (19.57 ± 4.1) are found to be almost same (difference not significant, p > 0.05) with the correlation coefficient 0.96, p < 0.0001. It was observed that any change/alterations in the pattern of RIP is followed by same amount of change/alterations in the pattern of PVDF nasal sensor with k = 0.815 indicating strong agreement between the PVDF nasal sensor and RIP respiratory air-flow pattern. The developed sensor is simple in design, non-invasive, patient friendly and hence shows promising routine clinical usage. The preliminary result shows that this new method can have various applications in respiratory monitoring and diagnosis. PMID:23771706

  1. A Real-time Method to Evaluate the Nasal Deposition and Clearance of Acetone in the Human Volunteer

    SciTech Connect

    Thrall, Karla D. ); Schwartz, Ronald E.; Weitz, Karl K. ); Soelberg, Jolen J. ); Foureman, Gary L.; Prah, James D.; Timchalk, Charles

    2003-05-01

    Nasal dosimetry models have become increasingly quantitative as insights into tissue deposition/clearance and computational fluid dynamics have become available. Validation of these models requires sufficient experimental data. However, investigations into respiratory deposition, particularly in human volunteers, have been historically limited due to methodological limitations. To overcome this, a method for evaluating the nasal wash-in, wash-out phenomena of a highly water-soluble compound in human volunteers was developed and characterized. This methodology was assessed using controlled human inhalation exposures to uniformly labeled 13C-acetone at approximately 1 ppm concentration for 30 minutes under different breathing maneuvers (inhale nose/exhale nose; inhale nose/exhale mouth; inhale mouth/exhale nose). A small-diameter air-sampling probe inserted in the nasopharyngeal cavity of the volunteer was connected directly to an ion-trap mass spectrometer capable of sampling every 0.8 sec. A second ion-trap mass spectrometer simultaneously sampled from the volunteer?s exhaled breath stream via a breath-inlet device interface. Together, the two mass spectrometers provided real-time appraisal of the 13C-acetone concentrations in the nasopharyngeal region and in the exhaled breath stream before, during, and after the different breathing maneuvers. The breathing cycle (depth and frequency) and heart rate were concurrently monitored throughout the exposure using a heart rate monitor and a human plethysmograph to differentiate inhalation and exhalation. Graphical overlay of the plethysmography results with the mass spectrometer measurements show clear quantifiable differences in 13C-acetone levels at the nasal probe as a function of breathing maneuvers. Breath-by-breath analysis of 13C-acetone concentrations indicate that between 40-75% of the compound is absorbed upon inhalation and nearly all of that absorbed released back into the breath stream during exhalation.

  2. Validation of Human Physiologically Based Pharmacokinetic Model for Vinyl Acetate Against Human Nasal Dosimetry Data

    SciTech Connect

    Hinderliter, Paul M.; Thrall, Karla D.; Corley, Rick A.; Bloemen, Louis J.; Bogdanffy, M S.

    2005-05-01

    Vinyl acetate has been shown to induce nasal lesions in rodents in inhalation bioassays. A physiologically based pharmacokinetic (PBPK) model for vinyl acetate has been used in human risk assessment, but previous in vivo validation was conducted only in rats. Controlled human exposures to vinyl acetate were conducted to provide validation data for the application of the model in humans. Five volunteers were exposed to 1, 5, and 10 ppm 13 C1 , 13 C2 vinyl acetate via inhalation. A probe inserted into thenasopharyngeal region sampled both 13 C1 , 13 C2 vinyl acetate and the major metabolite 13 C1 , 13 C2 acetaldehyde during rest and light exercise. Nasopharyngeal air concentrations were analyzed in real time by ion trap mass spectrometry (MS/MS). Experimental concentrations of both vinyl acetate and acetaldehyde were then compared to predicted concentrations calculated from the previously published human model. Model predictions of vinyl acetate nasal extraction compared favorably with measured values of vinyl acetate, as did predictions of nasopharyngeal acetaldehyde when compared to measured acetaldehyde. The results showed that the current PBPK model structure and parameterization are appropriate for vinyl acetate. These analyses were conducted from 1 to 10 ppm vinyl acetate, a range relevant to workplace exposure standards but which would not be expected to saturate vinyl acetate metabolism. Risk assessment based on this model further concluded that 24 h per day exposures up to 1 ppm do not present concern regarding cancer or non-cancer toxicity. Validation of the vinyl acetate human PBPK model provides support for these conclusions.

  3. In vivo imaging of functional microvasculature within tissue beds of oral and nasal cavities by swept-source optical coherence tomography with a forward/side-viewing probe

    PubMed Central

    Choi, Woo June; Wang, Ruikang K.

    2014-01-01

    We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS-OCT) at 1300 nm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm × 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions. PMID:25136490

  4. Essential role of peripheral node addressin in lymphocyte homing to nasal-associated lymphoid tissues and allergic immune responses

    PubMed Central

    Ohmichi, Yukari; Hirakawa, Jotaro; Imai, Yasuyuki; Fukuda, Minoru

    2011-01-01

    Nasal-associated lymphoid tissue (NALT) is a mucosal immune tissue that provides immune responses against inhaled antigens. Lymphocyte homing to NALT is mediated by specific interactions between lymphocytes and high endothelial venules (HEVs) in NALT. In contrast to HEVs in other mucosal lymphoid tissues, NALT HEVs strongly express peripheral node addressins (PNAds) that bear sulfated glycans recognized by the monoclonal antibody MECA-79. We investigated the role of PNAd in lymphocyte homing to NALT using sulfotransferase N-acetylglucosamine-6-O-sulfotransferase (GlcNAc6ST) 1 and GlcNAc6ST-2 double knockout (DKO) mice. The expression of PNAd in NALT HEVs was eliminated in DKO mice. Short-term homing assays indicated that lymphocyte homing to NALT was diminished by 90% in DKO mice. Production of antigen-specific IgE and the number of sneezes in response to nasally administered ovalbumin were also substantially diminished. Consistently, the NALT of DKO mice showed reduced production of IL-4 and increased production of IL-10 together with an increase in CD4+CD25+ regulatory T cells (Treg cells). Compared with the homing of CD4+CD25− conventional T cells, the homing of CD4+CD25+ Treg cells to NALT was less dependent on the L-selectin–PNAd interaction but was partially dependent on PSGL-1 (P-selectin glycoprotein ligand 1) and CD44. These results demonstrate that PNAd is essential for lymphocyte homing to NALT and nasal allergic responses. PMID:21518796

  5. Trade in human tissue products.

    PubMed

    Tonti-Filippini, Nicholas; Zeps, Nikolajs

    2011-03-01

    Trade in human tissue in Australia is prohibited by state law, and in ethical guidelines by the National Health and Medical Research Council: National statement on ethical conduct in human research; Organ and tissue donation by living donors: guidelines for ethical practice for health professionals. However, trade in human tissue products is a common practice especially for: reconstructive orthopaedic or plastic surgery; novel human tissue products such as a replacement trachea created by using human mesenchymal stem cells; biomedical research using cell lines, DNA and protein provided through biobanks. Cost pressures on these have forced consideration of commercial models to sustain their operations. Both the existing and novel activities require a robust framework to enable commercial uses of human tissue products while maintaining community acceptability of such practices, but to date no such framework exists. In this article, we propose a model ethical framework for ethical governance which identifies specific ethical issues such as: privacy; unique value of a person's tissue; commodification of the body; equity and benefit to the community; perverse incentives; and "attenuation" as a potentially useful concept to help deal with the broad range of subjective views relevant to whether it is acceptable to commercialise certain human tissue products. PMID:21382003

  6. Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells.

    PubMed

    Horváth, Tamás; Bartos, Csilla; Bocsik, Alexandra; Kiss, Lóránd; Veszelka, Szilvia; Deli, Mária A; Újhelyi, Gabriella; Szabó-Révész, Piroska; Ambrus, Rita

    2016-01-01

    The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations. PMID:27213303

  7. Attenuation of human nasal airway responses to bradykinin and histamine by inhibitors of nitric oxide synthase.

    PubMed Central

    Dear, J. W.; Ghali, S.; Foreman, J. C.

    1996-01-01

    1. The effects of inhibitors of nitric oxide synthase and local anaesthetics were studied on changes in human nasal airway patency and albumin extravasation in response to bradykinin and histamine, in vivo. 2. Compared with the action of the vasoconstrictor, ephedrine, 2.5 mumol, NG-nitro-L-arginine methyl ester (L-NAME), 1 mumol alone, did not change the resting value of the minimal cross-sectional area (A min) of the human nasal airway. L-NAME, 0.1 to 10 mumol, produced a dose-related inhibition of the reduction in A min caused by bradykinin, 300 micrograms. NG-monomethyl-L-arginine (L-NMMA), 1 mumol, similarly reduced the effect of bradykinin, 300 micrograms, on A min, but NG-nitro-D-arginine methyl ester (D-NAME), had no effect. L-NAME, 0.1 to 10 mumol, or L-NMMA, 10 mumol, failed to inhibit the effect of histamine, 300 micrograms on A min. 3. The inhibition by L-NAME, 1 mumol of the action of bradykinin, 300 micrograms on A min was maximal between 15 and 30 min after pretreatment with L-NAME. 4. L-NAME, 1 and 10 mumol, inhibited the extravasation of albumin into the nasal cavity induced by bradykinin, 300 micrograms, and also by histamine, 300 micrograms. D-NAME, 1 and 10 mumol had no effect on the extravasation of albumin in response to bradykinin or histamine. 5. L-Arginine, 30 mumol, reversed the effect of L-NAME, 1 mumol, on the bradykinin- and histamine-induced albumin extravasation into the nasal airway. 6. Local anaesthesia of the nasal airway with lignocaine, 10 mg, or benzocaine, 10 mg, failed to inhibit the reduction in A min or the albumin extravasation induced by either bradykinin, 300 micrograms, and histamine, 300 micrograms. 7. We conclude that the extravasation of plasma albumin caused by bradykinin and by histamine involves the generation of nitric oxide. The nasal blockage induced by bradykinin involves nitric oxide generation but the nasal blockage induced by histamine does not. PMID:8818341

  8. Cocaine inhibits extraneuronal O-methylation of exogenous norepinephrine in nasal and oral tissues of the rabbit

    SciTech Connect

    de la Lande, I.S.; Parker, D.A.S.; Proctor, C.H.; Marino, V.; Mackay-Sim, A.

    1987-11-30

    Nasal mucosa (respirator and olfactory) and lingual gingiva of the rabbit were depleted of their sympathetic nerves by superior cervical ganglionectomy. In the innervated nasal mucosa, exogenous tritiated norepinephrine (/sup 3/H-NE) was metabolized mainly to tritiated 3,4-dihydroxyphenylethylene glycol (/sup 3/HDOPEG) and 3,4-dihydroxy mandelic acid (/sup 3/HDOMA), whereas after denervation it was metabolized mainly to tritiated normetanephrine (/sup 3/HNMN). In the denervated mucosa, cocaine(30umol/l) inhibited /sup 3/HNMN formation by 50-60%. Cocaine also inhibited /sup 3/HNMN formation by 60% in the denervated lingual gingiva. It is concluded that the tissues metabolize /sup 3/H-NE via a cocaine-sensitive extraneuronal uptake and O-methylating system similar to that which has been shown to be present in dental pulp. 17 references, 1 table.

  9. Pilot study to establish a nasal tip prediction method from unknown human skeletal remains for facial reconstruction and skull photo superimposition as applied to a Japanese male populations.

    PubMed

    Utsuno, Hajime; Kageyama, Toru; Uchida, Keiichi; Kibayashi, Kazuhiko; Sakurada, Koichi; Uemura, Koichi

    2016-02-01

    Skull-photo superimposition is a technique used to identify the relationship between the skull and a photograph of a target person: and facial reconstruction reproduces antemortem facial features from an unknown human skull, or identifies the facial features of unknown human skeletal remains. These techniques are based on soft tissue thickness and the relationships between soft tissue and the skull, i.e., the position of the ear and external acoustic meatus, pupil and orbit, nose and nasal aperture, and lips and teeth. However, the ear and nose region are relatively difficult to identify because of their structure, as the soft tissues of these regions are lined with cartilage. We attempted to establish a more accurate method to determine the position of the nasal tip from the skull. We measured the height of the maxilla and mid-lower facial region in 55 Japanese men and generated a regression equation from the collected data. We obtained a result that was 2.0±0.99mm (mean±SD) distant from the true nasal tip, when applied to a validation set consisting of another 12 Japanese men. PMID:26724561

  10. Host innate inflammatory factors and staphylococcal protein A influence the duration of human Staphylococcus aureus nasal carriage

    PubMed Central

    Cole, Amy L.; Muthukrishnan, Gowrishankar; Chong, Christine; Beavis, Ashley; Eade, Colleen R.; Wood, Matthew P.; Deichen, Michael G.; Cole, Alexander M.

    2016-01-01

    Human Staphylococcus aureus (SA) nasal carriage provides a reservoir for the dissemination of infectious strains; however, factors regulating the establishment and persistence of nasal colonization are mostly unknown. We measured carriage duration and nasal fluid inflammatory markers after nasally inoculating healthy participants with their previously isolated SA strains. Ten out of 15 studies resulted in rapid clearance (9±6 days) that corresponded with upregulated chemokines, growth factors, and predominantly Th1-type cytokines, but not IL-17. Nasal SA persistence corresponded with elevated baseline levels of MIP-1β, IL-1β, and IL-6, no induction of inflammatory factors post-inoculation, and decreased IL-1RA:IL-1β ratio. SA-expressed staphylococcal protein A (SpA) levels correlated positively with carriage duration. Competitive inoculation studies revealed that isogenic SpA knockout (ΔSpA) strains were cleared faster than wild-type only in participants with upregulated inflammatory markers post-inoculation. The remaining participants did not mount an inflammatory response and did not clear either strain. ΔSpA strains demonstrated lower growth rates in carrier nasal fluids and lower survival rates when incubated with neutrophils. Collectively, the presented studies identify innate immune effectors that cooperatively modulate nasal carriage duration, and confirm SpA as a bacterial co-determinant of SA nasal carriage. PMID:26838052

  11. Excessive Fibrin Deposition in Nasal Polyps Caused by Fibrinolytic Impairment through Reduction of Tissue Plasminogen Activator Expression

    PubMed Central

    Takabayashi, Tetsuji; Kato, Atsushi; Peters, Anju T.; Hulse, Kathryn E.; Suh, Lydia A.; Carter, Roderick; Norton, James; Grammer, Leslie C.; Tan, Bruce K.; Chandra, Rakesh K.; Conley, David B.; Kern, Robert C.; Fujieda, Shigeharu

    2013-01-01

    Rationale: Nasal polyps (NPs) are characterized by intense edema or formation of pseudocysts filled with plasma proteins, mainly albumin. However, the mechanisms underlying NP retention of plasma proteins in their submucosa remain unclear. Objectives: We hypothesized that formation of a fibrin mesh retains plasma proteins in NPs. We assessed the fibrin deposition and expression of the components of the fibrinolytic system in patients with chronic rhinosinusitis (CRS). Methods: We assessed fibrin deposition in nasal tissue from patients with CRS and control subjects by means of immunofluorescence. Fibrinolytic components, d-dimer, and plasminogen activators were measured using ELISA, real-time PCR, and immunohistochemistry. We also performed gene expression and protein quantification analysis in cultured airway epithelial cells. Measurements and Main Results: Immunofluorescence data showed profound fibrin deposition in NP compared with uncinate tissue (UT) from patients with CRS and control subjects. Levels of the cross-linked fibrin cleavage product protein, d-dimer, were significantly decreased in NP compared with UT from patients with CRS and control subjects, suggesting reduced fibrinolysis (P < 0.05). Expression levels of tissue plasminogen activator (t-PA) mRNA and protein were significantly decreased in NP compared with UT from patients with CRS and control subjects (P < 0.01). Immunohistochemistry demonstrated clear reduction of t-PA in NP, primarily in the epithelium and glands. Th2 cytokine–stimulated cultured airway epithelial cells showed down-regulation of t-PA, suggesting a potential Th2 mechanism in NP. Conclusions: A Th2-mediated reduction of t-PA might lead to excessive fibrin deposition in the submucosa of NP, which might contribute to the tissue remodeling and pathogenesis of CRS with nasal polyps. PMID:23155140

  12. Hyperresponsiveness in the human nasal airway: new targets for the treatment of allergic airway disease.

    PubMed Central

    Turner, P J; Foreman, J C

    1999-01-01

    Allergic rhinitis is a condition which affects over 15% of the population in the United Kingdom. The pathological process involves two stages: nasal inflammation, and the development of nasal airway hyperresponsiveness (AHR) to allergen and a number of other stimuli. This results in the amplification of any subsequent allergic reaction, contributing to the chronic allergic state. A number of different hypotheses have been proposed to explain the underlying mechanism of AHR, including a role for eosinophil-derived proteins, free radicals and neuropeptides. While there may be a number of independent pathways which can result in AHR, evidence obtained from both animal models and in vivo experiments in humans indicate that some mediators may interact with one another, resulting in AHR. Further research into these interactions may open new avenues for the pharmacological treatment of chronic allergic rhinitis, and possibly other allergic airway diseases. PMID:10704051

  13. Determination of baseline human nasal pH and the effect of intranasally administered buffers.

    PubMed

    Washington, N; Steele, R J; Jackson, S J; Bush, D; Mason, J; Gill, D A; Pitt, K; Rawlins, D A

    2000-04-01

    The nose is becoming a common route of drug administration, however, little is known about the pH of the human nasal cavity. Local pH may have a direct effect on the rate and extent of absorption of ionizable compounds and hence this study was performed to investigate normal pH values and whether pH could be manipulated by various buffers. Twelve healthy volunteers participated in a study to measure pH in the anterior and posterior sites of the nasal cavity. Miniature pH electrodes were placed 3 cm apart in the nasal cavity and a baseline was recorded for 30 min once the pH had stabilized. One hundred microlitres of isotonic solution was sprayed into the nostril and the pH was measured for 4 h post-dose. The following five formulations were tested: formulation A--sodium chloride (0.9%) at pH 7.2; formulation B--sodium chloride (0.9%) at pH 5.8; formulation C--Sorensens phosphate buffer (0.06 M) at pH 5. 8; formulation D--Sorensens phosphate buffer (0.13 M) at pH 5.8 and formulation E--formulation as (c) but adjusted to pH 5.0. Each formulation also contained saccharin sodium (0.5%) as a taste marker for nasal clearance. The time at which each subject detected the taste of saccharin was noted. The 30-minute baseline recording prior to administration of the nasal spray formulation demonstrates that there was both considerable intersubject and intrasubject variation in nasal pH. The average pH in the anterior of the nose was 6.40 (+0. 11, -0.15 S.D.) when calculated from H(+) values. The pH in the posterior of the nasal cavity was 6.27 (+0.13, -0.18 S.D.). The overall range in pH was 5.17-8.13 for anterior pH and 5.20-8.00 for posterior pH. Formulation A caused the pH in the anterior part of the nasal cavity to reach a maximum of 7.06 in 11.25 min from the baseline of pH 6.14 (P<0.05). The mean baseline pH was 6.5 for the posterior part of the nose which did not change over the recording period. Formulation B caused the anterior pH to increase from pH 6. 60 to 7

  14. [Specific clinical and immunological features of chronic diseases of the nasal-associated lymphoid tissue in the children].

    PubMed

    Beniova, S N; Taranova, S V; Babko, S V

    2014-01-01

    The objective of the present work was to study the structure, clinical, and immunological features of various etiological variants of chronic diseases of the nasal-associated lymphoid tissue in the children. A total of 142 children at the age from 3 to 7 years presenting with this pathological condition were available for the observation. The study revealed differences in the clinical course of the disease and the cytokine response (IL-6, Ril-6, TNF, sYNFR55, sTNFR75) at the local and systemic levels for different pathogens (S. aureus, S. pneumoniae, S. pyrogenes). PMID:25377675

  15. A recovery method for airborne gunshot residue retained in human nasal mucus.

    PubMed

    Schwartz, R H; Zona, C A

    1995-07-01

    Each living person is equipped with their own personal particle filter, a nose. The human nose is capable of filtering and trapping airborne gunshot residue (AGSR) from discharged firearms. An extraction/concentration technique has been developed to recover the AGSR retained in human nasal mucus. The technique has successfully recovered abundant AGSR from 48 hours postfiring sample collection times. The AGSR particles were characterized by a JEOL 6400 scanning electron microscope coupled with a Noran Voyager energy dispersive X-ray spectrometer. PMID:7595306

  16. [Brown fat tissue in humans].

    PubMed

    Medvedev, L N; Elsukova, E I

    2002-01-01

    Brown adipose tissue (BAT) is universally present in mammals. Thermal production in such tissue is physiologically important for maintaining temperature homeostasis and regulation of body mass in small-size homoiotherms. At present it is clearly established that unlike other large mammals, brown adipose in man and primates is retained throughout the whole postnatal othogenesis. Therefore, BAT appears as a possible effector of pharmacogenetic protection from human excessive adiposis. Systematic reserach of various functioning aspects of this unique organ of mammals were started abroad as early as 1960-es, and are actively developing at present. Domestic research of energy circulation physiology and of thermoregulation developed mostly outside the brown adipose tissue. Therefore, the principal objective of this publication is to draw attention of experimental and clinical researches to an intriguing aspect of the issue of energy circulation in humans--the issue of brown adipose functioning. PMID:12004574

  17. RT-PCR detection of CYP1A1, 1A2, and 2E1 mRNAs in rat nasal tissue

    SciTech Connect

    Reddy, S.L.; Kim, S.G.; States, J.C.; Dahl, A.R.; Hotchkiss, J.; Novak, R.F. Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM )

    1991-03-15

    The expression of P450 in nasal tissue is of considerable importance given the exposure of these tissues to xenobiotics and the role of P450s in xenobiotic metabolism. CYP1A1, 1A2 and 2E1 mRNA expression was examined in olfactory tissue of rats exposed to 5 ppm pyridine 6 h daily for 4 d. RT-PCR was performed on poly(A){sup +} RNA using gene specific primers selected from published rat liver 1A1, 1A2 and 2E1 cDNAs. RT-PCR products derived from nasal mRNAs were detected and co-migrated with liver 1A1, 1A2 and 2W1 Rt-PCR products. Identical restriction patterns were obtained from HinfI and HpaII digests of nasal and liver 1A1 RT-PCR products; restriction digest patterns of nasal and liver 1A2 RT-PCR products were also identical. Southern analyses of nasal RT-PCR products, using liver 1A1 and 12 DNA probes, showed a single band suggesting considerable homology between nasal and liver 1A1 and 1A2 fragments. Cloning and sequencing of nasal 1A1, 1A2 and 2E1 RT-PCR products will confirm the identity of these gene products. These results show that 1A1, 1A2 and 2E1 mRNAs are expressed in rat olfactory tissue and suggest that the fragments examined share homology with those expressed in liver.

  18. Phenotype and function of nasal dendritic cells

    PubMed Central

    Lee, Haekyung; Ruane, Darren; Law, Kenneth; Ho, Yan; Garg, Aakash; Rahman, Adeeb; Esterházy, Daria; Cheong, Cheolho; Goljo, Erden; Sikora, Andrew G.; Mucida, Daniel; Chen, Benjamin; Govindraj, Satish; Breton, Gaëlle; Mehandru, Saurabh

    2015-01-01

    Intranasal vaccination generates immunity across local, regional and distant sites. However, nasal dendritic cells (DC), pivotal for the induction of intranasal vaccine- induced immune responses, have not been studied in detail. Here, using a variety of parameters, we define nasal DCs in mice and humans. Distinct subsets of “classical” DCs, dependent on the transcription factor zbtb46 were identified in the murine nose. The murine nasal DCs were FLT3 ligand-responsive and displayed unique phenotypic and functional characteristics including the ability to present antigen, induce an allogeneic T cell response and migrate in response to LPS or live bacterial pathogens. Importantly, in a cohort of human volunteers, BDCA-1+ DCs were observed to be the dominant nasal DC population at steady state. During chronic inflammation, the frequency of both BDCA-1+ and BDCA-3hi DCs was reduced in the nasal tissue, associating the loss of these immune sentinels with chronic nasal inflammation. The present study is the first detailed description of the phenotypic, ontogenetic and functional properties of nasal DCs and will inform the design of preventative immunization strategies as well as therapeutic modalities against chronic rhinosinusitis. PMID:25669151

  19. The influence of vegetative stimuli on the human nasal mucous membrane.

    PubMed

    Simon, H; Schmidt-Kloiber, H

    1985-03-01

    Measuring probes were inserted into the inferior nasal meatus in humans to record the effects of certain defined vegetative stimuli on the cavernous state and the temperature of the mucous membrane. An unilateral carotis compression induces a bilateral reactivity of the mucous membrane in the sense of a sympathicus stimulus. An unilateral bulbus pressure causes a bilateral reaction of the mucous membrane opposite to that of carotis compression. Blocking of the stellate ganglion produces a tonus reduction of the nervus sympathicus as was also found in animal experiments by other authors. Trigeminus stimulation induces a swelling of the nasal mucous membrane, whereas a voluntary breathing stop causes decongestion. Facial blushing, the only undefined and involuntary stimulus, is followed by an unswelling and a decrease of mucous membrane temperature. The results of our investigations are in agreement with analogous animal experiments. This is not surprising as man has a vegetative nervous system which is essentially unchanged from the beginning of evolutionary development. Only blushing is an expression of a reaction behaviour characteristic of human beings only. PMID:4001756

  20. Phenotypic and functional characteristics of IL-21-expressing CD8+ T cells in human nasal polyps

    PubMed Central

    Xiao, Li; Jia, Lei; Bai, Lu; He, Long; Yang, Binyan; Wu, Changyou; Li, Huabin

    2016-01-01

    Although CD4+ T cells are recognized to play an important role in the inflammatory response of nasal polyps (NPs), the biological functions of CD8+ T cells in polypogenesis remain unclear. In this study, we analyzed cell markers, cytokine expression and transcription factors in IL-21-expressing CD8+ T cells in polyp tissues of NP patients. The results showed that the majority of IL-21-producing CD8+ T cells were effector memory cells and they co-expressed IFN-γ. IL-21-expressing CD8+ T cells in polyp tissues expressed higher CXCR5, PD-1, and ICOS levels than cells in control tissues and showed significantly higher T-bet and Bcl-6 expression levels compared with IL-21−CD8+ T cells. Purified polyp CD8+ T cells promoted IgG production from isolated polyp B cells in vitro, and recombinant IL-12 modulated the expression of IL-21, IFN-γ and CD40L in purified polyp CD8+ T cells. Moreover, the percentage of IL-21+CD8+ T cells in polyp tissues was positively correlated with endoscopic and CT scan scores in NP patients. These findings indicated that polyp CD8+ T cells, by co-expressing IL-21 and IFN-γ and other markers, display a Tfh cell functionality, which is associated with the clinical severity of NP patients. PMID:27468819

  1. Phenotypic and functional characteristics of IL-21-expressing CD8(+) T cells in human nasal polyps.

    PubMed

    Xiao, Li; Jia, Lei; Bai, Lu; He, Long; Yang, Binyan; Wu, Changyou; Li, Huabin

    2016-01-01

    Although CD4(+) T cells are recognized to play an important role in the inflammatory response of nasal polyps (NPs), the biological functions of CD8(+) T cells in polypogenesis remain unclear. In this study, we analyzed cell markers, cytokine expression and transcription factors in IL-21-expressing CD8(+) T cells in polyp tissues of NP patients. The results showed that the majority of IL-21-producing CD8(+) T cells were effector memory cells and they co-expressed IFN-γ. IL-21-expressing CD8(+) T cells in polyp tissues expressed higher CXCR5, PD-1, and ICOS levels than cells in control tissues and showed significantly higher T-bet and Bcl-6 expression levels compared with IL-21(-)CD8(+) T cells. Purified polyp CD8(+) T cells promoted IgG production from isolated polyp B cells in vitro, and recombinant IL-12 modulated the expression of IL-21, IFN-γ and CD40L in purified polyp CD8(+) T cells. Moreover, the percentage of IL-21(+)CD8(+) T cells in polyp tissues was positively correlated with endoscopic and CT scan scores in NP patients. These findings indicated that polyp CD8(+) T cells, by co-expressing IL-21 and IFN-γ and other markers, display a Tfh cell functionality, which is associated with the clinical severity of NP patients. PMID:27468819

  2. Nonneoplastic nasal lesions in rats and mice.

    PubMed Central

    Monticello, T M; Morgan, K T; Uraih, L

    1990-01-01

    Rodents are commonly used for inhalation toxicology studies, but until recently the nasal passages have often been overlooked or only superficially examined. The rodent nose is a complex organ in which toxicant-induced lesions may vary, depending on the test compound. A working knowledge of rodent nasal anatomy and histology is essential for the proper evaluation of these responses. Lack of a systematic approach for examining rodent nasal tissue has led to a paucity of information regarding nonneoplastic lesions in the rodent nose. Therefore, slides from the National Toxicology Program (NTP) and the Chemical Industry Institute of Toxicology (CIIT) were examined, and the literature was reviewed to assemble the spectrum of nonneoplastic rodent nasal pathology. Presented are lesions associated with the various types of epithelia lining the rodent nasal cavity plus lesions involving accessory nasal structures. Even though there are anatomic and physiologic differences between the rodent and human nose, both rats and mice provide valuable animal models for the study of nasal epithelial toxicity, following administration of chemical compounds. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PLATE 17. PLATE 18. PLATE 19. PLATE 20. PLATE 21. PLATE 22. PLATE 23. PLATE 24. PLATE 25. PLATE 26. PLATE 27. PLATE 28. PLATE 29. PLATE 30. PLATE 31. PLATE 32. PLATE 33. PLATE 34. PLATE 35. PLATE 36. PLATE 37. PLATE 38. PMID:2200665

  3. Numerical simulation of airflow and micro-particle deposition in human nasal airway pre- and post-virtual sphenoidotomy surgery.

    PubMed

    Bahmanzadeh, Hojat; Abouali, Omid; Faramarzi, Mohammad; Ahmadi, Goodarz

    2015-06-01

    In the present study, the effects of endoscopic sphenoidotomy surgery on the flow patterns and deposition of micro-particles in the human nasal airway and sphenoid sinus were investigated. A realistic model of a human nasal passage including nasal cavity and paranasal sinuses was constructed using a series of CT scan images of a healthy subject. Then, a virtual sphenoidotomy by endoscopic sinus surgery was performed in the left nasal passage and sphenoid sinus. Transient airflow patterns pre- and post-surgery during a full breathing cycle (inhalation and exhalation) were simulated numerically under cyclic flow condition. The Lagrangian approach was used for evaluating the transport and deposition of inhaled micro-particles. An unsteady particle tracking was performed for the inhalation phase of the breathing cycle for the case that particles were continuously entering into the nasal airway. The total deposition pattern and sphenoid deposition fraction of micro-particles were evaluated and compared for pre- and post-surgery cases. The presented results show that sphenoidotomy increased the airflow into the sphenoid sinus, which led to increased deposition of micro-particles in this region. Particles up to 25 μm were able to penetrate into the sphenoid in the post-operation case, and the highest deposition in the sphenoid for the resting breathing rate occurred for 10 μm particles at about 1.5%. PMID:25862997

  4. Detection of novel Chlamydiae and Legionellales from human nasal samples of healthy volunteers.

    PubMed

    Corsaro, Daniele; Venditti, Danielle

    2015-07-01

    Chlamydiae are intracellular bacterial parasites of eukaryotes, ranging from amoebae to humans. They comprise many novel members and are investigated as emerging pathogens. Environmental studies highlighted similarities between the ecologies of chlamydiae and legionellae, both groups being important agents of respiratory infections. Herein, we analyzed nasal samples from healthy persons, searching for the presence of amoebae, chlamydiae and legionellae. From a total of 25 samples, we recovered by PCR eight samples positive to chlamydiae and six samples positive to legionellae. Among these samples, four were positive to both organisms. The sequencing of 16S rDNAs allowed to identify (i) among Chlamydiae: Parachlamydia acanthamoebae, Chlamydophila psittaci, Chlamydophila felis, and members of Rhabdochlamydiaceae, Simkaniaceae and E6 lineage and (ii) among Legionellaceae: Legionella longbeachae, Legionella bozemanii and Legionella impletisoli. Unexpectedly, we also recovered Diplorickettsia sp. Amoebae collected from nasal mucosae, Acanthamoeba and Vermamoeba, were endosymbiont-free, and chlamydiae revealed refractory to amoeba coculture. This study shows common exposure to chlamydiae and legionellae and suggests open air activities like gardening as a probable additional source of infection. PMID:25697709

  5. Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage

    SciTech Connect

    Koren, H.S.; Devlin, R.B.

    1992-01-01

    A set of symptoms has been described during the past two decades which has been called the sick building syndrome. These symptoms include eye, nose, and throat irritation; headache; mental fatigue; and respiratory distress. It is likely that volatile organic compounds (VOC) present in synthetic materials used in homes and office buildings contribute to these symptoms. However, there have been few studies in which humans have been exposed to known amounts of VOC under carefully controlled conditions. In the study 14 subjects have been exposed to a mixture of VOC (25 mg/cu m total hydrocarbon) representative of what is found in new homes and office buildings. Since irritation of the nose and throat are symptoms often associated with the upper respiratory tract and may result from an inflammatory response in the upper airways, the authors have used nasal lavage to monitor neutrophil (PMN) influx into the nasal passages following exposure to VOC. The authors report statistically significant increases in PMNs both immediately after a four hour exposure to VOC, as well as 18 hours later.

  6. In vivo microvascular imaging of human oral and nasal cavities using swept-source optical coherence tomography with a single forward/side viewing probe

    NASA Astrophysics Data System (ADS)

    Choi, Woo June; Wang, Ruikang K.

    2015-03-01

    We report three-dimensional (3D) imaging of microcirculation within human cavity tissues in vivo using a high-speed swept-source optical coherence tomography (SS-OCT) at 1.3 μm with a modified probe interface. Volumetric structural OCT images of the inner tissues of oral and nasal cavities are acquired with a field of view of 2 mm x 2 mm. Two types of disposable and detachable probe attachments are devised and applied to the port of the imaging probe of OCT system, enabling forward and side imaging scans for selective and easy access to specific cavity tissue sites. Blood perfusion is mapped with OCT-based microangiography from 3D structural OCT images, in which a novel vessel extraction algorithm is used to decouple dynamic light scattering signals, due to moving blood cells, from the background scattering signals due to static tissue elements. Characteristic tissue anatomy and microvessel architectures of various cavity tissue regions of a healthy human volunteer are identified with the 3D OCT images and the corresponding 3D vascular perfusion maps at a level approaching capillary resolution. The initial finding suggests that the proposed method may be engineered into a promising tool for evaluating and monitoring tissue microcirculation and its alteration within a wide-range of cavity tissues in the patients with various pathological conditions.

  7. Immunochemical characterization of multiple forms of cytochrome P-450 in rabbit nasal microsomes and evidence for tissue-specific expression of P-450s NMa and NMb.

    PubMed

    Ding, X X; Coon, M J

    1990-04-01

    Two unique forms of cytochrome P-450 (P-450), designated NMa and NMb, were recently isolated in this laboratory from nasal microsomes of rabbits. In the present study, polyclonal antibodies to the purified nasal cytochromes were prepared. Immunochemical analysis with specific rabbit anti-NMa and sheep anti-NMb antibodies indicated that P-450 isozymes identical to or having a high structural homology with NMa are present in both olfactory and respiratory mucosa, as well as in liver, but NMb was detected only in the olfactory mucosa. Neither form was detected in other tissues examined, including brain, esophageal mucosa, heart, intestinal mucosa, kidney, and lung. The specific occurrence of NMb in the olfactory mucosa was further substantiated by the detection and specific inhibition by anti-NMb of the formation of unique NMb-dependent metabolites of testosterone in olfactory microsomes but not in microsomes from liver or respiratory mucosa. Similar experiments with antibodies to previously purified rabbit hepatic P-450 isozymes indicated that not all of the hepatic cytochromes are expressed in the nasal tissues. Thus, P-450 isozymes structurally homologous to hepatic forms 2, 3a, and 4, but not 3b and 6, were found in the olfactory mucosa. On the other hand, only form 2 was detected in the respiratory mucosa. Immunoquantitation experiments revealed that NMa and NMb are the major P-450 forms in olfactory microsomes, whereas NMa and P-450 form 2 (or its homolog) constitute the major portion of the respiratory nasal microsomal P-450. The level of NMa in the liver is relatively low, accounting for less than 3% of total microsomal P-450 in this tissue. In addition, evidence is provided that NMa is the major catalyst in the dealkylation of two nasal carcinogens, hexamethylphosphoramide and phenacetin, in both olfactory and respiratory nasal microsomes. PMID:2109181

  8. Transport and Deposition of Welding Fume Agglomerates in a Realistic Human Nasal Airway.

    PubMed

    Tian, Lin; Inthavong, Kiao; Lidén, Göran; Shang, Yidan; Tu, Jiyuan

    2016-07-01

    Welding fume is a complex mixture containing ultra-fine particles in the nanometer range. Rather than being in the form of a singular sphere, due to the high particle concentration, welding fume particles agglomerate into long straight chains, branches, or other forms of compact shapes. Understanding the transport and deposition of these nano-agglomerates in human respiratory systems is of great interest as welding fumes are a known health hazard. The neurotoxin manganese (Mn) is a common element in welding fumes. Particulate Mn, either as soluble salts or oxides, that has deposited on the olfactory mucosa in human nasal airway is transported along the olfactory nerve to the olfactory bulb within the brain. If this Mn is further transported to the basal ganglia of the brain, it could accumulate at the part of the brain that is the focal point of its neurotoxicity. Accounting for various dynamic shape factors due to particle agglomeration, the current computational study is focused on the exposure route, the deposition pattern, and the deposition efficiency of the inhaled welding fume particles in a realistic human nasal cavity. Particular attention is given to the deposition pattern and deposition efficiency of inhaled welding fume agglomerates in the nasal olfactory region. For particles in the nanoscale, molecular diffusion is the dominant transport mechanism. Therefore, Brownian diffusion, hydrodynamic drag, Saffman lift force, and gravitational force are included in the model study. The deposition efficiencies for single spherical particles, two kinds of agglomerates of primary particles, two-dimensional planar and straight chains, are investigated for a range of primary particle sizes and a range of number of primary particles per agglomerate. A small fraction of the inhaled welding fume agglomerates is deposited on the olfactory mucosa, approximately in the range 0.1-1%, and depends on particle size and morphology. The strong size dependence of the deposition

  9. Reconstituted Human Upper Airway Epithelium as 3-D In Vitro Model for Nasal Polyposis

    PubMed Central

    de Borja Callejas, Francisco; Martínez-Antón, Asunción; Alobid, Isam; Fuentes, Mireya; Cortijo, Julio; Picado, César

    2014-01-01

    Background Primary human airway epithelial cells cultured in an air-liquid interface (ALI) develop a well-differentiated epithelium. However, neither characterization of mucociliar differentiation overtime nor the inflammatory function of reconstituted nasal polyp (NP) epithelia have been described. Objectives 1st) To develop and characterize the mucociliar differentiation overtime of human epithelial cells of chronic rhinosinusitis with nasal polyps (CRSwNP) in ALI culture system; 2nd) To corroborate that 3D in vitro model of NP reconstituted epithelium maintains, compared to control nasal mucosa (NM), an inflammatory function. Methods Epithelial cells were obtained from 9 NP and 7 control NM, and differentiated in ALI culture for 28 days. Mucociliary differentiation was characterized at different times (0, 7, 14, 21, and 28 days) using ultrastructure analysis by electron microscopy; ΔNp63 (basal stem/progenitor cell), β-tubulin IV (cilia), and MUC5AC (goblet cell) expression by immunocytochemistry; and mucous (MUC5AC, MUC5B) and serous (Lactoferrin) secretion by ELISA. Inflammatory function of ALI cultures (at days 0, 14, and 28) through cytokine (IL-8, IL-1β, IL-6, IL-10, TNF-α, and IL-12p70) and chemokine (RANTES, MIG, MCP-1, IP-10, eotaxin-1, and GM-CSF) production was analysed by CBA (Cytometric Bead Array). Results In both NP and control NM ALI cultures, pseudostratified epithelium with ciliated, mucus-secreting, and basal cells were observed by electron microscopy at days 14 and 28. Displaying epithelial cell re-differentation, β-tubulin IV and MUC5AC positive cells increased, while ΔNp63 positive cells decreased overtime. No significant differences were found overtime in MUC5AC, MUC5B, and lactoferrin secretions between both ALI cultures. IL-8 and GM-CSF were significantly increased in NP compared to control NM regenerated epithelia. Conclusion Reconstituted epithelia from human NP epithelial cells cultured in ALI system provides a 3D in vitro model

  10. Protocol for a human in vivo model of acute cigarette smoke inhalation challenge in smokers with COPD: monitoring the nasal and systemic immune response using a network biology approach

    PubMed Central

    Ross, Clare L; Galloway-Phillipps, Neil; Armstrong, Paul C; Mitchell, Jane A; Warner, Timothy D; Brearley, Christopher; Ito, Mari; Tunstall, Tanushree; Elkin, Sarah; Kon, Onn Min; Hansel, Trevor T; Paul-Clark, Mark J

    2015-01-01

    Introduction Cigarette smoke contributes to a diverse range of diseases including chronic obstructive pulmonary disease (COPD), cardiovascular disorders and many cancers. There currently is a need for human challenge models, to assess the acute effects of a controlled cigarette smoke stimulus, followed by serial sampling of blood and respiratory tissue for advanced molecular profiling. We employ precision sampling of nasal mucosal lining fluid by absorption to permit soluble mediators measurement in eluates. Serial nasal curettage was used for transcriptomic analysis of mucosal tissue. Methods and analysis Three groups of strictly defined patients will be studied: 12 smokers with COPD (GOLD Stage 2) with emphysema, 12 matched smokers with normal lung function and no evidence of emphysema, and 12 matched never smokers with normal spirometry. Patients in the smoking groups are current smokers, and will be given full support to stop smoking immediately after this study. In giving a controlled cigarette smoke stimulus, all patients will have abstained from smoking for 12 h, and will smoke two cigarettes with expiration through the nose in a ventilated chamber. Before and after inhalation of cigarette smoke, a series of samples will be taken from the blood, nasal mucosal lining fluid and nasal tissue by curettage. Analysis of plasma nicotine and metabolites in relation to levels of soluble inflammatory mediators in nasal lining fluid and blood, as well as assessing nasal transcriptomics, ex vivo blood platelet aggregation and leucocyte responses to toll-like receptor agonists will be undertaken. Implications Development of acute cigarette smoke challenge models has promise for the study of molecular effects of smoking in a range of pathological processes. Ethics and dissemination This study was approved by the West London National Research Ethics Committee (12/LO/1101). The study findings will be presented at conferences and will be reported in peer-reviewed journals

  11. Dosimetry of nasal uptake of soluble and reactive gases: A first study of inter-human variability (Journal Article)

    EPA Science Inventory

    Anatomically accurate human child and adult nasal tract models will be used in concert with computationally simulated air flow information to investigate the influence of age-related differences in anatomy on inhalation dosimetry in the upper and lower airways. The findings of t...

  12. Radiation Effect on Human Tissue

    NASA Technical Reports Server (NTRS)

    Richmond, Robert C.; Cruz, Angela; Bors, Karen; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Predicting the occurrence of human cancer following exposure of an epidemiologic population to any agent causing genetic damage is a difficult task. To an approximation, this is because the uncertainty of uniform exposure to the damaging agent, and the uncertainty of uniform processing of that damage within a complex set of biological variables, degrade the confidence of predicting the delayed expression of cancer as a relatively rare event within clinically normal individuals. This situation begs the need for alternate controlled experimental models that are predictive for the development of human cancer following exposures to agents causing genetic damage. Such models historically have not been of substantial proven value. It is more recently encouraging, however, that developments in molecular and cell biology have led to an expanded knowledge of human carcinogenesis, and of molecular markers associated with that process. It is therefore appropriate to consider new laboratory models developed to accomodate that expanded knowledge in order to assess the cancer risks associated with exposures to genotoxic agents. When ionizing radiation of space is the genotoxic agent, then a series of additional considerations for human cancer risk assessment must also be applied. These include the dose of radiation absorbed by tissue at different locations in the body, the quality of the absorbed radiation, the rate at which absorbed dose accumulates in tissue, the way in which absorbed dose is measured and calculated, and the alterations in incident radiation caused by shielding materials. It is clear that human cancer risk assessment for damage caused by ionizing radiation is a multidisciplinary responsibility, and that within this responsibility no single discipline can hold disproportionate sway if a risk assessment model of radiation-induced human cancer is to be developed that has proven value. Biomolecular and cellular markers from the work reported here are considered

  13. Effects of pH and dose on nasal absorption of scopolamine hydrobromide in human subjects

    NASA Technical Reports Server (NTRS)

    Ahmed, S.; Sileno, A. P.; deMeireles, J. C.; Dua, R.; Pimplaskar, H. K.; Xia, W. J.; Marinaro, J.; Langenback, E.; Matos, F. J.; Putcha, L.; Romeo, V. D.; Behl, C. R.

    2000-01-01

    PURPOSE: The present study was conducted to evaluate the effects of formulation pH and dose on nasal absorption of scopolamine hydrobromide, the single most effective drug available for the prevention of nausea and vomiting induced by motion sickness. METHODS: Human subjects received scopolamine nasally at a dose of 0.2 mg/0.05 mL or 0.4 mg/0.10 mL, blood samples were collected at different time points, and plasma scopolamine concentrations were determined by LC-MS/MS. RESULTS: Following administration of a 0.2 mg dose, the average Cmax values were found to be 262+/-118, 419+/-161, and 488+/-331 pg/ mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At the 0.4 mg dose the average Cmax values were found to be 503+/-199, 933+/-449, and 1,308+/-473 pg/mL for pH 4.0, 7.0, and 9.0 formulations, respectively. At a 0.2 mg dose, the AUC values were found to be 23,208+/-6,824, 29,145+/-9,225, and 25,721+/-5,294 pg x min/mL for formulation pH 4.0, 7.0, and 9.0, respectively. At a 0.4 mg dose, the average AUC value was found to be high for pH 9.0 formulation (70,740+/-29,381 pg x min/mL) as compared to those of pH 4.0 (59,573+/-13,700 pg x min/mL) and pH 7.0 (55,298+/-17,305 pg x min/mL) formulations. Both the Cmax and AUC values were almost doubled with doubling the dose. On the other hand, the average Tmax, values decreased linearly with a decrease in formulation pH at both doses. For example, at a 0.4 mg dose, the average Tmax values were 26.7+/-5.8, 15.0+/-10.0, and 8.8+/-2.5 minutes at formulation pH 4.0, 7.0, and 9.0, respectively. CONCLUSIONS: Nasal absorption of scopolamine hydrobromide in human subjects increased substantially with increases in formulation pH and dose.

  14. The modulation of tissue-specific gene expression in rat nasal chondrocyte cultures by bioactive glasses.

    PubMed

    Asselin, Audrey; Hattar, Susan; Oboeuf, Martine; Greenspan, David; Berdal, Ariane; Sautier, Jean-Michel

    2004-11-01

    Since bone repair may occur, following endochondral ossification, we have investigated the behaviour of chondrocytes isolated from nasal septum cartilage of foetal rats and cultured up to 21 days in the presence of a melt-derived bioactive glass (Bioglass 45S5) and a less reactive glass with 60 wt% silica content (60S). In both cultures, chondrocytes proliferate and form typical cartilaginous nodules on day 5 of cultures. However, on day 12, the nodules in contact with 45S5 granules became darker than in 60S cultures, corresponding to the emergence of matrix biomineralization. Transmission electron microscopy showed a collagen-rich matrix composed of densely packed fibres and mineralized foci formed of needle-shaped crystals in contact with an electron-dense layer located at the periphery of the material. The specific activity of alkaline phosphatase was significant higher in 45S5 cultures on day 15 than in 60S cultures. Real time RT-PCR was used to monitor gene expression levels of specific chondrogenic markers. The transcription factor Sox9 was expressed throughout the culture period, but with no significant differences between the two kinds of cultures. In contrast, Runx2 expression was higher in experiment cultures on day 12. Type II collagen mRNA and aggrecan, showed an almost similar expression pattern with a strong expression at the beginning of cultures but higher in experiment cultures. Indian hedgehog was strongly expressed between day 9 and 12 with a significant stimulation in 45S5 cultures. Similarly, type X collagen mRNA seemed to be up-regulated in 45S5 cultures on day 20. In conclusion, this study shows hat 45S5 Bioglass has the ability to support the growth of chondrocytes and to stimulate some chondrogenic molecular markers. PMID:15159078

  15. Airflow, gas deposition, and lesion distribution in the nasal passages

    SciTech Connect

    Morgan, K.T.; Monticello, T.M. )

    1990-04-01

    The nasal passages of laboratory animals and man are complex, and lesions induced in the delicate nasal lining by inhaled air pollutants vary considerably in location and nature. The distribution of nasal lesions is generally a consequence of regional deposition of the inhaled material, local tissue susceptibility, or a combination of these factors. Nasal uptake and regional deposition are are influenced by numerous factors including the physical and chemical properties of the inhaled material, such as water solubility and reactivity; airborne concentration and length of exposure; the presence of other air contaminants such as particulate matter; nasal metabolism, and blood and mucus flow. For certain highly water-soluble or reactive gases, nasal airflow patterns play a major role in determining lesion distribution. Studies of nasal airflow in rats and monkeys, using casting and molding techniques combined with a water-dye model, indicate that nasal airflow patterns are responsible for characteristic differences in the distribution of nasal lesions induced by formaldehyde in these species. Local tissue susceptibility is also a complex issue that may be a consequence of many factors, including physiologic and metabolic characteristics of the diverse cell populations that comprise each of the major epithelial types lining the airways. Identification of the principal factors that influence the distribution and nature of nasal lesions is important when attempting the difficult process of determining potential human risks using data derived from laboratory animals. Toxicologic pathologists can contribute to this process by carefully identifying the site and nature of nasal lesions induced by inhaled materials. 61 references.

  16. Correlation between nasal membrane permeability and nasal absorption rate.

    PubMed

    Zhang, Hefei; Lin, Chih-Wei; Donovan, Maureen D

    2013-03-01

    The objective of this study was to investigate the relationship between in vitro permeability (Papp) values obtained from isolated nasal tissues and the absorption rates (ka) of the same compounds following nasal administration in animals and humans. The Papp of a set of 11 drug compounds was measured using animal nasal explants and plasma time-concentration profiles for each of the same compounds following intravenous (IV) and intranasal (IN) administration were experimentally determined or obtained from literature reports. The plasma clearance was estimated from the IV plasma time-concentration profiles, and ka was determined from the IN plasma time-concentration profiles using a deconvolution approach. The level of correlation between Papp and ka was established using Pearson correlation analysis. A good correlation (r=0.77) representing a point-to-point relationship for each of the compounds was observed. This result indicates that the nasal absorption for many drug candidates can be estimated from a readily measured in vitro Papp value. PMID:23225081

  17. Silver resistance in MRSA isolated from wound and nasal sources in humans and animals.

    PubMed

    Loh, Jia V; Percival, Steven L; Woods, Emma J; Williams, Nicola J; Cochrane, Christine A

    2009-02-01

    Methicillin-resistant Staphylococcus aureus (MRSA) colonises skin, nasal passages and dermal wounds. Methods used to manage wounds infected and colonised with MRSA often include the use of topical antiseptics such as ionic silver and iodine. The objectives of this study were to determine the prevalence of silver-resistance (sil) genes in MRSA and methicillin-resistant coagulase-negative staphylococci (MR-CNS) isolated from wounds and nasal cavities of humans and animals, and also to determine the susceptibility of sil-positive and sil-negative MRSA isolates to a silver-containing Hydrofiber (SCH) wound dressing, on planktonic silE-positive and silE-negative MRSA. Polymerase chain reaction was used to determine the presence of three silver-resistance (sil) genes, silE, silP and silS in 33 MRSA and 8 methicillin-resistant staphylococci (MR-CNS). SilP and silS genes were absent in all isolates tested; however, two MRSA strains were found to contain the silE gene, together with one isolate of MR-CNS. Phenotypic resistance of the silE-positive strains and their susceptibility to the SCH dressing was evaluated using the zone of inhibition test on Mueller Hinton agar, and confocal laser microscopy using a live/dead fluorescent stain. Results confirmed that the SCH dressing was effective in killing all MRSA strains with and without the silE gene. First, this study showed that the prevalence of sil genes was low in the isolates investigated; and secondly, that the presence of a silver-resistance gene (silE) in MRSA and MR-CNS did not afford protection to the organism in the presence of a SCH wound dressing. The use of topical antiseptics in chronic wound care should be considered before the use of antibiotics that can result in their overuse and the risk of further resistance. PMID:19291113

  18. Permeation and pathways of human calcitonin (hCT) across excised bovine nasal mucosa.

    PubMed

    Lang, S; Rothen-Rutishauser, B; Perriard, J C; Schmidt, M C; Merkle, H P

    1998-01-01

    In vitro permeation of human calcitonin (hCT), salmon calcitonin (sCT), and the somatostatin analog octreotide (SMS) through excised bovine nasal mucosa was studied applying donor/receiver experiments and confocal laser scanning microscopy. Permeabilities of gonadorelin, buserelin, Hoe013, and of thymopoietin fragments TP5 and TP4 were also included. Apparent permeability coefficients (Peff) ranged between 4 x 10(-5) (SMS) and 1.7 x 10(-5) cm s(-1) (TP4). Such Peff are typical for leaky-type airway epithelia. The order of permeabilities was: SMS > hCT, sCT > buserelin, Hoe013 > TP5 > TP4, LHRH. The relatively high permeability of hCT and sCT contrasted to their high molecular weight. At 37 degrees C, the permeability of hCT from mucosal to serosal (m-to-s) was found two-fold higher (p < 0.05) than from serosal to mucosal (s-to-m). Controls using 3H-mannitol showed equal permeabilities in both directions. At 4 degrees C, permeation of hCT was reduced but equal in both directions (m-to-s and s-to-m). As evaluated by confocal laser scanning microscopy, uptake studies with FITC-18-hCT revealed intracellular fluorescence in the epithelial cells, at 10 min/10 microM exposure in the form of fluorescent vesicles. By combination of these findings, an endocytotic pathway is suggested to contribute to the transport of hCT through nasal epithelium. PMID:9533651

  19. EFFECT OF DIESEL EXHAUST PARTICLES ON HUMAN NASAL LAVAGE CELLS AND DNA ADDUCTS

    EPA Science Inventory

    The overall aim of this study is to determine (using a nasal challenge model) the effect of diesel exhaust particles (DEP) on nasal responses including induction of inflammation, immune changes and DNA damage. We are also examining how treatment of DEP with ozone (oz-DEP)modify ...

  20. Comments on recent data for particle deposition in human nasal passages

    SciTech Connect

    Martonen, T.B.; Zhang, Z.

    1992-01-01

    The deposition of inhaled particles within human nasal passages has important toxicologic and pharmacologic applications. However, experimental data quantitating factors affecting particle deposition are rare. The authors have evaluated findings from investigations employing either replica nasopharyngeal (NP) casts or surrogate model airways and compared them to each other and to human subject results. For ultrafine particles, studies using casts and models are incompatible, measured deposition values from the latter being lower by an entire order of magnitude. Possible sources of discrepancies between the data are suggested herein. Studies with diverse NP replicates, however, have yielded consistent deposition data over a wide particle size range, about 0.005 - 7 micrometers. Cast experiments underestimate, but in a systematic manner, in vivo information over a 0.5 - 3 micrometers interval. It is recommended, therefore, that NP replica cast data, rather than NP model airway data, be used to simulate human passages. For extrapolation modeling purposes, an original empirical formula based upon a logistic theory is derived which describes deposition over a particle size range of three orders of magnitude.

  1. Nasal Cancer

    MedlinePlus

    ... the way to your throat as you breathe. Cancer of the nasal cavity and paranasal sinuses is ... be like those of infections. Doctors diagnose nasal cancer with imaging tests, lighted tube-like instruments that ...

  2. Oxidative stress and acute changes in murine brain tissues after nasal instillation of copper particles with different sizes.

    PubMed

    Liu, Yang; Gao, Yuxi; Liu, Ying; Li, Bai; Chen, Chunying; Wu, Gang

    2014-06-01

    We aim to investigate the biological effects of copper particles on the murine brain and their underlying mechanism after nasal instillation of copper particles. We choose different sizes and different concentrations of copper nanoparticles for mice intranasal use. Within one week, the mice were sacrificed. Pathological lesions of glial cells were detected by immunohistochemical assay. Immunohistochemical assay reveals that glial fibrillary acidic protein (GFAP) increased significantly in all experimental groups, especially in nanocopper groups. The ultrastructure of nerve cells was observed through TEM, whose results show that there were chromatin congregation and mitochondria shrinkage in the olfactory cells, and that there was increase of endoplasmic reticulum and disassociation of endoplasmic reticulum ribosomes in hippocampus, particularly in the nanocopper-groups. Oxidative stress indexes were determined with colorimetric methods. There was no significant increase in the antioxidative enzymes (GPX, GST, SOD) in brain tissues; however, significant increase of malondiadehyde (MDA) contents was only found in the Cu nanoparticle-exposed mice at the high dose of 40 mg per kg body weight. Based on the investigation into the biological effects of copper nanoparticles (23.5 nm) after intranasal instillation to the mice, we have found that copper particles can indeed enter into the olfactory bulb and then the deeper brain. The inhalation of high dose copper nanoparticles can induce severer lesions of brain in the experimental mice. The underlying mechanism of copper nanoparticles causing severe brain damage bears little connection with oxidative stress. PMID:24738425

  3. Biomarkers of inflammation in ozone-exposed humans: Comparison of the nasal and bronchoalveolar lavage

    SciTech Connect

    Graham, D.E.; Koren, H.S.

    1989-06-01

    An influx of neutrophils (PMNs), a primary feature of acute inflammation, has been associated with the development of lower lung disorders, such as emphysema and idiopathic fibrosis, as well as airway hyperreactivity and increased mucus secretion. It was previously established that an acute inflammatory response in the upper respiratory tract of humans could be studied by analysis of nasal lavages (NL), which is inexpensive, non-invasive, and atraumatic. However, the relationship of the cellular changes in the upper respiratory tract to changes in the lower airways has not been thoroughly investigated in humans. Here the cellular changes detected in the NL with those detected in the bronchoalveolar lavage (BAL) taken from the same individual have been compared. Ten subjects were exposed to either filtered air or 0.4 ppm ozone (O3), with exercise, for 2 hrs. The NL was done prior to, immediately following an 18 hr post exposure, while the BAL was done only at 18 hr post exposure. A significant increase in PMNs was detected in the NL immediately post exposure to 03, (7.7-fold increase; p=.003), and remained elevated in the 18 hr post-03 NL (6.1-fold increase; p<.001).

  4. A critical review of the influence of oxytocin nasal spray on social cognition in humans: evidence and future directions.

    PubMed

    Guastella, Adam J; Graustella, Adam J; MacLeod, Colin

    2012-03-01

    The past eight years of research has demonstrated that oxytocin nasal spray has a significant impact on human social cognition. The aim of this review is to provide critical comment on the literature using an information-processing framework. We provide a summary of fundamental assumptions of information-processing models and highlight an impressive range of consistent findings that demonstrate the impact of oxytocin nasal spray on social information processing. These findings include that oxytocin nasal spray improves the early conceptual detection of affect from social cues and improves the accurate appraisal of affect from social cues at elaborate and strategic levels of processing. There is some evidence that these effects may be particularly powerful for positive social cues. This review comments on inconsistent results that have been reported. We argue that such inconsistencies can, in part, be explained by variability across experiments in the degree to which potential extraneous confounds have been controlled, the different methods upon which studies assessed cognition, and the extent to which the focus of investigation has been on group-based outcomes. Finally, we argue that sound cognitive experimental methods can provide powerful tools to identify markers of response to oxytocin nasal spray that can be integrated into more complex circuitry models. The identification of robust markers has particular value in predicting behavioral and therapeutic response to intervention. This should now be a major focus for future research. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior. PMID:22265852

  5. Human Rhinovirus-induced Proinflammatory Cytokine and Interferon-β Responses in Nasal Epithelial Cells From Chronic Rhinosinusitis Patients

    PubMed Central

    Kim, Ji Heui; Kim, You-Sun; Cho, Gye Song; Kim, Nam Hee; Gong, Chang-Hoon; Lee, Bong-Jae

    2015-01-01

    Purpose Asthma exacerbation from human rhinovirus (HRV) infection is associated with deficient antiviral interferon (IFN) secretion. Although chronic rhinosinusitis (CRS), an inflammatory upper airway disease, is closely linked to asthma, IFN-β responses to HRV infections in human nasal epithelial cells (HNECs) from CRS patients remain to be studied. We evaluated inflammatory and antiviral responses to HRV infection in HNECs from CRS patients. Methods HNECs, isolated from turbinate tissue of 13 patients with CRS and 14 non-CRS controls, were infected with HRV16 for 4 hours. The HRV titer, LDH activity, production of proinflammatory cytokines and IFN-β proteins, and expression levels of RIG-I and MDA5 mRNA were assessed at 8, 24, and 48 hours after HRV16 infection. Results The reduction in viral titer was slightly delayed in the CRS group compared to the non-CRS control group. IL-6 and IL-8 were significantly increased to a similar extent in both groups after HRV infection. In the control group, IFN-β production and MDA5 mRNA expression were significantly increased at 8 and 24 hours after HRV16 infection, respectively. By contrast, in the CRS group, IFN-β was not induced by HRV infection; however, HRV-induced MDA5 mRNA expression was increased, but the increase was slightly delayed compared to the non-CRS control group. The RIG-I mRNA level was not significantly increased by HRV16 infection in either group. Conclusions HRV-induced secretion of proinflammatory cytokines in CRS patients was not different from that in the non-CRS controls. However, reductions in viral titer, IFN-β secretion, and MDA5 mRNA expression in response to HRV infection in CRS patients were slightly impaired compared to those in the controls, suggesting that HRV clearance in CRS patients might be slightly deficient. PMID:26122508

  6. Enhancing Effect of Borneol and Muscone on Geniposide Transport across the Human Nasal Epithelial Cell Monolayer

    PubMed Central

    Chen, Zhenzhen; Gong, Xin; Lu, Yang; Du, Shouying; Yang, Zhihui; Bai, Jie; Li, Pengyue; Wu, Huichao

    2014-01-01

    Geniposide is widely used in the treatment of cerebral ischemic stroke and cerebrovascular diseases for its anti-thrombotic and anti-inflammatory effects. Recent studies demonstrated that geniposide could be absorbed promptly and thoroughly by intranasal administration in mice and basically transported into the brain. Here, we explored its transport mechanism and the effect of borneol and muscone on its transport by human nasal epithelial cell (HNEC) monolayer. The cytotoxicity of geniposide, borneol, muscone and their combinations on HNECs was evaluated by the MTT assay. Transcellular transport of geniposide and the influence of borneol and muscone were studied using the HNEC monolayer. Immunostaining and transepithelial electrical resistance were measured to assess the integrity of the monolayer. The membrane fluidity of HNEC was evaluated by fluorescence recovery after photobleaching. Geniposide showed relatively poor absorption in the HNEC monolayer and it was not a P-gp substrate. Geniposide transport in both directions significantly increased when co-administrated with increasing concentrations of borneol and muscone. The enhancing effect of borneol and muscone on geniposide transport across the HNEC may be attributed to the significant enhancement on cell membrane fluidity, disassembly effect on tight junction integrity and the process was reversible. These results indicated that intranasal administration has good potential to treat cerebrovascular diseases. PMID:24992195

  7. Human upper respiratory tract responses to inhaled pollutants with emphasis on nasal lavage

    SciTech Connect

    Koren, H.S.; Devlin, R.B. )

    1992-04-30

    A set of symptoms has been described during the past two decades. These symptoms, which have been called the sick building syndrome, include eye, nose, and throat irritation; headache; mental fatigue; and respiratory distress. It is likely that VOCs present in synthetic materials used in homes and office buildings contribute to these symptoms. There have been few studies, however, in which humans have been exposed to known amounts of VOCs under carefully controlled conditions. In this study, 14 subjects have been exposed to a mixture of VOCs (25 mg/m3 total hydrocarbon) representative of what is found in new homes and office buildings. Because irritation of the nose and throat are symptoms often associated with the upper respiratory tract and may result from an inflammatory response in the upper airways, we have used NAL to monitor PMN influx into the nasal passages following exposure to VOCs. We report statistically significant increases in PMNs both immediately after a 4-hr exposure to VOCs, as well as 18 hr later.

  8. Assessment of cell surface glycoconjugates in normal, benign and malignant human nasal mucosa.

    PubMed

    Fang, S Y; Ohyama, M

    1997-12-01

    Aberrant glycosylation of proteins is a common characteristic of neoplastic changes. No reports exist relating cell surface glycoconjugates to normal, benign and malignant human nasal mucosa. Using lectin affinity histochemistry, glycoconjugate reactivities for peanut agglutinin (PNA), concanavalin A (Con A), Griffonia simplicifolia agglutinin II (GSA-II), soy bean agglutinin (SBA) and Ulex europaeus agglutinin l (UEA-I) were analysed in the following groups: normal, benign (polyp, papilloma, and inverted papilloma) and malignant (squamous cell carcinoma (SCC) alone, SCC arising in inverted papilloma, and adenocarcinoma). The positive rate of lectin staining was evaluated using a quantitative AutoCAD programme. We correlated glycoconjugate expression to clinical features, diagnosis, and malignant transformation. The positive rate of PNA after neuraminidase pre-treatment (NA-PNA) staining was higher in inverted papilloma, while all-negative in polyp and papilloma. NA-PNA staining may be used as a differential diagnostic tool. Both inverted papilloma portions and SCC portions of the SCC synchronized with inverted papilloma subjects showed similar Con A and NA-PNA staining patterns. The biological characteristics define inverted papilloma as a pre-malignant neoplasm. The positive rate of PNA staining was significantly higher in inverted papilloma (inverted papilloma transformed to SCC) compared to inverted papilloma alone. Hence, PNA staining may predict malignant transformation of inverted papilloma. However, further investigations are required to prove this possibly worthwhile prognostic marker. PMID:9532636

  9. Oxymetazoline Nasal Spray

    MedlinePlus

    Afrin® Nasal Spray ... Anefrin® Nasal Spray ... Dristan® Nasal Spray ... Mucinex® Nasal Spray ... Nostrilla® Nasal Spray ... Vicks Sinex® Nasal Spray ... Zicam® Nasal Spray ... Oxymetazoline nasal spray is used to relieve nasal discomfort caused by colds, allergies, and hay fever. It is also used to ...

  10. Expression of ICAM-1 in nasal epithelium and levels of soluble ICAM-1 in nasal lavage fluid during human experimental rhinovirus infection.

    PubMed

    Winther, Birgit; Arruda, Eurico; Witek, Theodore J; Marlin, Steven D; Tsianco, Michael M; Innes, Donald J; Hayden, Frederick G

    2002-02-01

    Most rhinovirus serotypes use intercellular adhesion molecule-1 (ICAM-1) as the receptor to enter cells, but ICAM-1 expression has not been detected on normal nasal epithelial cells. During experimental rhinovirus infection, expression of ICAM-1 on nasal epithelial cells was examined with immunohistochemical staining of nasal scrape biopsy specimens, and levels of soluble ICAM-1 in nasal lavage fluid were measured by sandwich enzyme-linked immunosorbent assay technique. Expression of ICAM-1 on nasal epithelial cells increased following inoculation in 20 of 23 infected subjects. The median number of ICAM-1-positive cells per 6.25-mm(2) area of stained biopsy specimen was 0 in control samples (day 20 or 33 after inoculation), and in those without infection, 6 on day 1 (P< or =.05), 14.5 on day 3 (P< or =.01), 1.5 on day 5, and 0 on day 9. In a different group of volunteers, soluble ICAM-1 in nasal lavage fluid was higher on days 1 and 3 compared with preinoculation levels (P< or =.001), but only 11 of 23 infected subjects had a 2-fold or greater increase. Up-regulation of ICAM-1 receptor expression on nasal epithelial cells occurred within 24 hours after inoculation in experimental rhinovirus infections (prior to onset of symptoms) and declined promptly by day 5. PMID:11843719

  11. Nasal packing and stenting

    PubMed Central

    Weber, Rainer K.

    2011-01-01

    Nasal packs are indispensable in ENT practice. This study reviews current indications, effectiveness and risks of nasal packs and stents. In endoscopic surgery, nasal packs should always have smooth surfaces to minimize mucosal damage, improve wound healing and increase patient comfort. Functional endoscopic endonasal sinus surgery allows the use of modern nasal packs, since pressure is no longer required. So called hemostatic/resorbable materials are a first step in this direction. However, they may lead to adhesions and foreign body reactions in mucosal membranes. Simple occlusion is an effective method for creating a moist milieu for improved wound healing and avoiding dryness. Stenting of the frontal sinus is recommended if surgery fails to produce a wide, physiologically shaped drainage path that is sufficiently covered by intact tissue. PMID:22073095

  12. α-Klotho Expression in Human Tissues

    PubMed Central

    Lim, Kenneth; Groen, Arnoud; Molostvov, Guerman; Lu, Tzongshi; Lilley, Kathryn S.; Snead, David; James, Sean; Wilkinson, Ian B.; Ting, Stephen

    2015-01-01

    Context: α-Klotho has emerged as a powerful regulator of the aging process. To date, the expression profile of α-Klotho in human tissues is unknown, and its existence in some human tissue types is subject to much controversy. Objective: This is the first study to characterize systemwide tissue expression of transmembrane α-Klotho in humans. We have employed next-generation targeted proteomic analysis using parallel reaction monitoring in parallel with conventional antibody-based methods to determine the expression and spatial distribution of human α-Klotho expression in health. Results: The distribution of α-Klotho in human tissues from various organ systems, including arterial, epithelial, endocrine, reproductive, and neuronal tissues, was first identified by immunohistochemistry. Kidney tissues showed strong α-Klotho expression, whereas liver did not reveal a detectable signal. These results were next confirmed by Western blotting of both whole tissues and primary cells. To validate our antibody-based results, α-Klotho-expressing tissues were subjected to parallel reaction monitoring mass spectrometry (data deposited at ProteomeXchange, PXD002775) identifying peptides specific for the full-length, transmembrane α-Klotho isoform. Conclusions: The data presented confirm α-Klotho expression in the kidney tubule and in the artery and provide evidence of α-Klotho expression across organ systems and cell types that has not previously been described in humans. PMID:26280509

  13. N-acetylcysteine inhibits Na+ absorption across human nasal epithelial cells.

    PubMed

    Rochat, Thierry; Lacroix, Jean-Silvain; Jornot, Lan

    2004-10-01

    N-acetylcysteine (NAC) is a widely used mucolytic drug in patients with a variety of respiratory disorders. The mechanism of action is based on rupture of the disulfide bridges of the high molecular glycoproteins present in the mucus, resulting in smaller subunits of the glycoproteins and reduced viscosity of the mucus. Because Na(+) absorption regulates airway surface liquid volume and thus the efficiency of mucociliary clearance, we asked whether NAC affects the bioelectric properties of human nasal epithelial cells. A 24-h basolateral treatment with 10 mM of NAC decreased the transepithelial potential difference and short-circuit current (I(SC)) by 40%, and reduced the amiloride-sensitive current by 50%, without affecting the transepithelial resistance. After permeabilization of the basolateral membranes of cells with amphotericin B in the presence of a mucosal-to-serosal Na(+) gradient (135:25 mM), NAC inhibited 45% of the amiloride-sensitive current. The Na(+)-K(+)-ATPase pump activity and the basolateral K(+) conductance were not affected by NAC treatment. NAC did not alter total cell mRNA and protein levels of alpha-epithelial Na(+) channel (EnaC) subunit, but reduced abundance of alpha-ENaC subunits in the apical cell membrane as quantified by biotinylation. This effect can be ascribed to the sulphydryl (SH) group of NAC, since N-acetylserine and S-carboxymethyl-l-cysteine were ineffective. Given the importance of epithelial Na(+) channels in controlling the thin layer of fluid that covers the surface of the airways, the increase in the fluidity of the airway mucus following NAC treatment in vivo might be in part related to downregulation of Na(+) absorption and consequently water transport. PMID:15281093

  14. Nasal commensal Staphylococcus epidermidis counteracts influenza virus

    PubMed Central

    Chen, Hui-Wen; Liu, Pei-Feng; Liu, Yu-Tsueng; Kuo, Sherwin; Zhang, Xing-Quan; Schooley, Robert T.; Rohde, Holger; Gallo, Richard L.; Huang, Chun-Ming

    2016-01-01

    Several microbes, including Staphylococcus epidermidis (S. epidermidis), a Gram-positive bacterium, live inside the human nasal cavity as commensals. The role of these nasal commensals in host innate immunity is largely unknown, although bacterial interference in the nasal microbiome may promote ecological competition between commensal bacteria and pathogenic species. We demonstrate here that S. epidermidis culture supernatants significantly suppressed the infectivity of various influenza viruses. Using high-performance liquid chromatography together with mass spectrometry, we identified a giant extracellular matrix-binding protein (Embp) as the major component involved in the anti-influenza effect of S. epidermidis. This anti-influenza activity was abrogated when Embp was mutated, confirming that Embp is essential for S. epidermidis activity against viral infection. We also showed that both S. epidermidis bacterial particles and Embp can directly bind to influenza virus. Furthermore, the injection of a recombinant Embp fragment containing a fibronectin-binding domain into embryonated eggs increased the survival rate of virus-infected chicken embryos. For an in vivo challenge study, prior Embp intranasal inoculation in chickens suppressed the viral titres and induced the expression of antiviral cytokines in the nasal tissues. These results suggest that S. epidermidis in the nasal cavity may serve as a defence mechanism against influenza virus infection. PMID:27306590

  15. Use of human tissue explants to study human infectious agents

    PubMed Central

    Grivel, Jean-Charles; Margolis, Leonid

    2012-01-01

    The study of human cell–cell and cell–pathogen interactions that occur in the context of complex tissue cytoarchitecture is critical for deciphering the mechanisms of many normal and pathogenic processes. This protocol describes methods for culturing and infecting explants of human tissues to study the pathogenesis of human infectious agents and their local interactions. The protocol relies on the use of fresh human tissues dissected into small blocks or biopsies that are cultured at the liquid–air interface on collagen rafts. These tissue blocks retain their cytoarchitecture and support productive infection of various pathogens without exogenous stimulation. Experimental details for setting up cultures of human tonsils, lymph nodes and cervicovaginal and rectosigmoid tissues, including protocols for their infection with HIV-1 and other pathogens, are described here. Using this protocol, culture and infections can be set up in 3–6 h and be maintained for 2–3 weeks, depending on the tissue used. PMID:19197269

  16. Differential Response of Human Nasal and Bronchial Epithelial Cells upon Exposure to Size-fractionated Dairy Dust

    PubMed Central

    Hawley, Brie; Schaeffer, Joshua; Poole, Jill A.; Dooley, Gregory P.; Reynolds, Stephen; Volckens, John

    2015-01-01

    Exposure to organic dusts is associated with increased respiratory morbidity and mortality in agricultural workers. Organic dusts in dairy farm environments are complex, polydisperse mixtures of toxic and immunogenic compounds. Previous toxicological studies focused primarily on exposures to the respirable size fraction, however, organic dusts in dairy farm environments are known to contain larger particles. Given the size distribution of dusts from dairy farm environments, the nasal and bronchial epithelia represent targets of agricultural dust exposures. In this study, well-differentiated normal human bronchial epithelial cells and human nasal epithelial cells were exposed to two different size fractions (PM10 and PM>10) of dairy parlor dust using a novel aerosol-to-cell exposure system. Levels of pro-inflammatory transcripts (IL-8, IL-6, and TNF-α) were measured two hr after exposure. Lactate dehydrogenase (LDH) release was also measured as an indicator of cytotoxicity. Cell exposure to dust was measured in each size fraction as a function of mass, endotoxin, and muramic acid levels. To our knowledge, this is the first study to evaluate the effects of distinct size fractions of agricultural dust on human airway epithelial cells. Our results suggest that both PM10 and PM>10 size fractions elicit a pro-inflammatory response in airway epithelial cells and that the entire inhalable size fraction needs to be considered when assessing potential risks from exposure to agricultural dusts. Further, data suggest that human bronchial cells respond differently to these dusts than human nasal cells and, therefore, the two cell types need to be considered separately in airway cell models of agricultural dust toxicity. PMID:25965193

  17. Grating-based tomography of human tissues

    NASA Astrophysics Data System (ADS)

    Müller, Bert; Schulz, Georg; Mehlin, Andrea; Herzen, Julia; Lang, Sabrina; Holme, Margaret; Zanette, Irene; Hieber, Simone; Deyhle, Hans; Beckmann, Felix; Pfeiffer, Franz; Weitkamp, Timm

    2012-07-01

    The development of therapies to improve our health requires a detailed knowledge on the anatomy of soft tissues from the human body down to the cellular level. Grating-based phase contrast micro computed tomography using synchrotron radiation provides a sensitivity, which allows visualizing micrometer size anatomical features in soft tissue without applying any contrast agent. We show phase contrast tomography data of human brain, tumor vessels and constricted arteries from the beamline ID 19 (ESRF) and urethral tissue from the beamline W2 (HASYLAB/DESY) with micrometer resolution. Here, we demonstrate that anatomical features can be identified within brain tissue as well known from histology. Using human urethral tissue, the application of two photon energies is compared. Tumor vessels thicker than 20 μm can be perfectly segmented. The morphology of coronary arteries can be better extracted in formalin than after paraffin embedding.

  18. Nasal-associated lymphoid tissue is a site of long-term virus-specific antibody production following respiratory virus infection of mice.

    PubMed

    Liang, B; Hyland, L; Hou, S

    2001-06-01

    Nasal immunoglobulin A provides an initial defense against inhaled respiratory pathogens. However, it is not known whether the nasal-associated lymphoid tissues (NALT) are able to mount an effective long-lasting pathogen-specific immune response, nor is it known whether functional differences exist between the organized NALT (O-NALT) and the diffuse NALT lining the nasal passages (D-NALT). Here we show that although both the O-NALT and the D-NALT are capable of producing virus-specific antibody in response to influenza virus infection, the frequency of specific antibody-forming cells in the D-NALT is much greater than the frequency observed in the O-NALT. Furthermore, we show that the D-NALT but not the O-NALT is the site of long-term virus-specific humoral immunity which lasts for the life of the animal. These results indicate that the D-NALT is not only the major effector site of the NALT but also the site of local long-term specific antibody production. PMID:11333927

  19. Foxg1 is required to limit the formation of ciliary margin tissue and Wnt/β-catenin signalling in the developing nasal retina of the mouse.

    PubMed

    Fotaki, Vassiliki; Smith, Rowena; Pratt, Thomas; Price, David J

    2013-08-15

    The ciliary margin (CM) develops in the peripheral retina and gives rise to the iris and the ciliary body. The Wnt/β-catenin signalling pathway has been implicated in ciliary margin development. Here, we tested the hypothesis that in the developing mouse retina Foxg1 is responsible for suppressing the Wnt/β-catenin pathway and restricting CM development. We showed that there is excess CM tissue in Foxg1(-/-) null embryos and this expansion is more pronounced in the nasal retina where Foxg1 normally shows its highest expression levels. Results on expression of a reporter allele for Wnt/β-catenin signalling and of Lef1, a target of Wnt/β-catenin signalling, displayed significant upregulation of this pathway in Foxg1(-/-) nulls at embryonic days 12.5 and 14.5. Interestingly, this upregulation was observed specifically in the nasal retina, where normally very few Wnt-responsive cells are observed. These results indicate a suppressive role of Foxg1 on this signalling pathway. Our results reveal a new role of Foxg1 in limiting CM development in the nasal peripheral retina and add a new molecular player in the developmental network involved in CM specification. PMID:23624311

  20. NCI’s Cooperative Human Tissue Network

    Cancer.gov

    Quality biospecimens are a foundational resource for cancer research. One of NCI’s longest running biospecimen programs is the Cooperative Human Tissue Network, a resource mainly for basic discovery and early translational research.

  1. Airflow in the Human Nasal Passage and Sinuses of Chronic Rhinosinusitis Subjects

    PubMed Central

    Kumar, Haribalan; Jain, Ravi; Douglas, Richard G.; Tawhai, Merryn H.

    2016-01-01

    Endoscopic surgery is performed on patients with chronic inflammatory disease of the paranasal sinuses to improve sinus ventilation. Little is known about how sinus surgery affects sinonasal airflow. In this study nasal passage geometry was reconstructed from computed tomographic imaging from healthy normal, pre-operative, and post-operative subjects. Transient air flow through the nasal passage during calm breathing was simulated. Subject-specific differences in ventilation of the nasal passage were observed. Velocity magnitude at ostium was different between left and right airway. In FESS, airflow in post-surgical subjects, airflow at the maxillary sinus ostium was upto ten times higher during inspiration. In a Lothrop procedure, airflow at the frontal sinus ostium can be upto four times higher during inspiration. In both post-operative subjects, airflow at ostium was not quasi-steady. The subject-specific effect (of surgery) on sinonasal interaction evaluated through airflow simulations may have important consequences for pre- and post-surgical assessment and surgical planning, and design for improvement of the delivery efficiency of nasal therapeutics. PMID:27249219

  2. Different reactions of human nasal and Eustachian tube mucosa after hyperbaric oxygen exposure: a pilot study.

    PubMed

    Mutzbauer, Till S; Neubauer, Birger; Tetzlaff, Kay

    2013-03-01

    Impairment of Eustachian tube function has been observed after hyperbaric oxygen treatment as well as after diving on oxygen used as breathing gas. The aim of the present study was to evaluate the influence of hyperbaric oxygen exposure on Eustachian tube ventilatory function and airflow characteristics of the nose. Six police task force divers performing two consecutive dives within a regular training schedule on oxygen were examined. Middle ear impedance, and nasal airflow velocities before and after diving as well as on the morning after the dive day were measured. Middle ear impedance decreased overnight in comparison to pre-dive values (P = 0.027) as well as compared to the value after the first dive (P = 0.032). Rhinoflowmetry did not reveal any changes of nasal airflow velocities related to the dives. Furthermore, no association between middle ear impedance and nasal airflow velocities was found. An impairment of Eustachian tube ventilatory function was obtained after hyperbaric oxygen exposure during dives employing oxygen as breathing gas. This impairment, however, was not associated with altered airflow characteristics of divers' noses. Thus, it seems unlikely that hyperbaric oxygen exerts an effect on the nasal mucosa similar to that on the Eustachian tube mucosa. PMID:22829159

  3. Variation in alternative splicing across human tissues

    PubMed Central

    Yeo, Gene; Holste, Dirk; Kreiman, Gabriel; Burge, Christopher B

    2004-01-01

    Background Alternative pre-mRNA splicing (AS) is widely used by higher eukaryotes to generate different protein isoforms in specific cell or tissue types. To compare AS events across human tissues, we analyzed the splicing patterns of genomically aligned expressed sequence tags (ESTs) derived from libraries of cDNAs from different tissues. Results Controlling for differences in EST coverage among tissues, we found that the brain and testis had the highest levels of exon skipping. The most pronounced differences between tissues were seen for the frequencies of alternative 3' splice site and alternative 5' splice site usage, which were about 50 to 100% higher in the liver than in any other human tissue studied. Quantifying differences in splice junction usage, the brain, pancreas, liver and the peripheral nervous system had the most distinctive patterns of AS. Analysis of available microarray expression data showed that the liver had the most divergent pattern of expression of serine-arginine protein and heterogeneous ribonucleoprotein genes compared to the other human tissues studied, possibly contributing to the unusually high frequency of alternative splice site usage seen in liver. Sequence motifs enriched in alternative exons in genes expressed in the brain, testis and liver suggest specific splicing factors that may be important in AS regulation in these tissues. Conclusions This study distinguishes the human brain, testis and liver as having unusually high levels of AS, highlights differences in the types of AS occurring commonly in different tissues, and identifies candidate cis-regulatory elements and trans-acting factors likely to have important roles in tissue-specific AS in human cells. PMID:15461793

  4. Melanin content of hamster tissues, human tissues, and various melanomas

    SciTech Connect

    Watts, K.P.; Fairchild, R.G.; Slatkin, D.N.; Greenberg, D.; Packer, S.; Atkins, H.L.; Hannon, S.J.

    1981-02-01

    Melanin content (percentage by weight) was determined in both pigmented and nonpigmented tissues of Syrian golden hamsters bearing Greene melanoma. Melanin content was also measured in various other melanoma models (B-16 in C57 mice, Harding-Passey in BALB/c mice, and KHDD in C3H mice) and in nine human melanomas, as well as in selected normal tissues. The purpose was to evaluate the possible efficacy of chlorpromazine, which is known to bind to melanin, as a vehicle for boron transport in neutron capture therapy. Successful therapy would depend upon selective uptake and absolute concentration of borated compounds in tumors; these parameters will in turn depend upon melanin concentration in melanomas and nonpigmented ''background'' tissues. Hamster whole eyes, hamster melanomas, and other well-pigmented animal melanomas were found to contain 0.3 to 0.8% melanin by weight, whereas human melanomas varied from 0.1 to 0.9% (average, 0.35%). Other tissues, with the exception of skin, were lower in content by a factor of greater than or equal to30. Melanin pigment was extracted from tissues, and the melanin content was determined spectrophotometrically. Measurements were found to be sensitive to the presence of other proteins. Previous procedures for isolating and quantifying melanin often neglected the importance of removing proteins and other interfering nonmelanic substances.

  5. Human histocultures (tissue explants) in retrovirology

    PubMed Central

    Arakelyan, Anush; Fitzgerald, Wendy; Grivel, Jean-Charles; Vanpouille, Christophe; Margolis, Leonid

    2014-01-01

    Summary Viral pathogenesis is studied predominantly in cultures of primary isolated cells or cell lines. Many retroviruses efficiently replicate only in activated cells. Therefore, in order to become efficient viral producers cells should be artificially activated, a procedure which significantly changes cell physiology. However, for many viral diseases, like HIV-1 and other retroviruses’ diseases, critical pathogenic events occur in tissues and cell isolation from their native microenvironment prevents single cell cultures from faithfully reflecting important aspects of cell-cell and cell-pathogen interactions that occur in the context of complex tissue cytoarchitecture. Tissue explants (histocultures) that retain tissue cytoarchitecture and many aspects of cell-cell interactions more faithfully represent in vivo tissue features. Human histocultures constitute an adequate model for studying viral pathogenesis under controlled laboratory conditions. Protocols for various human histocultures as applied to study retroviral pathogenesis, in particular of HIV-1, have been refined by our laboratory and are described in the present publication. Human histocultures of human tonsils and lymph nodes, as well as of recto-sigmoid and cervico-vaginal tissues can be used to study viral transmission, pathogenesis and as a pre-clinical platform for antivirals evaluation. PMID:24158827

  6. Nasal Physiology

    MedlinePlus

    ... nose is constantly exposed to inhaled debris and microbes (viruses, bacteria, and fungus). The respiratory system has ... Mucus is designed to trap inhaled particles (including microbes) that are subsequently cleared from the airways. Nasal ...

  7. Nasal polyps

    MedlinePlus

    ... BS, Burks AW, et al, eds. Middleton's Allergy: Principles and Practice . 8th ed. Philadelphia, PA: Elsevier Saunders; 2014:chap 43. Becker SS. Surgical management of polyps in the treatment of nasal airway ...

  8. Nasal Cancer

    MedlinePlus

    Your paranasal sinuses are small hollow spaces around the nose. They are lined with cells that make mucus, which keeps your nose from drying out. The nasal cavity is the passageway just behind your ...

  9. Nasal passages of Göttingen minipigs from the neonatal period to young adult.

    PubMed

    Kuper, C Frieke; Ernst, Heinrich; van Oostrum, Lidy C M; Rittinghausen, Susanne; Penninks, André H; Ganderup, Niels-Christian; Wolterbeek, André P M

    2012-06-01

    Histopathological examination of the nasal passages requires a standardized approach for recording lesion distribution patterns. Nasal diagrams provide guidance to map the lesions. Information on lesions exists for rodents, dogs, and monkeys, which all have been used in inhalation studies. Recently, minipigs have garnered interest as an inhalation model because minipigs resemble humans in many features of anatomy, physiology, and biochemistry and may be a good alternative to monkeys and dogs. The present work explored the microanatomy and histology of the nasal passages of Göttingen minipigs from postnatal day 1 until 6 months of age. Six nasal levels were selected, which allow examination of the squamous, transitional (nonciliated) and ciliated respiratory, and olfactory epithelia; the nasopharynx; and relevant structures such as the vomeronasal organ, olfactory bulb, and nasal/nasopharynx-associated lymphoid tissue. PMID:22301951

  10. Bradykinin metabolism in rat and sheep nasal secretions.

    PubMed

    Chung, F Y; Donovan, M D

    1995-07-01

    The nasal secretions are the first barrier that nasally administered drugs encounter. Therefore, the characterization of peptide metabolism in the nasal secretions is essential to predict nasal peptide bioavailability. Metabolism of bradykinin was measured in rat and sheep nasal secretions to estimate the extent of degradation of nasally administered peptide compounds. A single-pass, in situ nasal perfusion technique was employed to collect secretions for the investigation of peptide metabolism in rat nasal secretions. The protein content, mucin concentration, and degree of bradykinin metabolism in perfusate aliquots collected over a 2-h period showed that the early perfusate fractions contained most of the active secretory materials. Evidence of continuous mucus secretion and plasma extravasation was found in the nasal perfusate throughout the entire collection period. Sheep nasal secretions were collected with a cotton pledget inserted into the nasal cavity. Bradykinin and its fragments were degraded by carboxypeptidases and endopeptidases present in both rat and sheep nasal secretions. Hydrolysis of Phe5-Ser6 was the major metabolism pathway of bradykinin in the rat nasal perfusate, whereas in sheep nasal secretions, hydrolysis of the Pro7-Phe8 and Phe8-Arg9 bonds also occurred. Evidence of angiotensin converting enzyme, carboxypeptide N, and aminopeptidase activity was identified in the rat nasal perfusate with specific substrates and inhibitors. The activity of these and other enzymes in the nasal secretions may significantly limit the bioavailability of nasally administered peptide drugs prior to their exposure to the nasal mucosal tissues. PMID:7562432

  11. Modulation of TNF and GM-CSF release from dispersed human nasal polyp cells and human whole blood by inhibitors of different PDE isoenzymes and glucocorticoids.

    PubMed

    Marx, Degenhard; Tassabehji, Mahmoud; Heer, Sabine; Hüttenbrink, K-B; Szelenyi, Istvan

    2002-01-01

    The aim of this study was to investigate the role of the inhibitors of different PDE isoenzymes (PDE 1-5) on the production of two pro-inflammatory cytokines - tumor necrosis factor alpha (TNF) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Two in vitro models were used to compare the antiinflammatory properties of PDE inhibitors with that of glucocorticoids. The effect on TNF release from diluted human blood following lipopolysaccharide (LPS from Salmonella abortus equi) stimulation as well as the GM-CSF and TNF release from human nasal polyp cells following allergic stimulation were investigated. Both models proofed to be well suited for the characterisation of the antiinflammatory properties of new chemical entities. In diluted human blood and dispersed human nasal polyp cells the induced TNF release was most potently suppressed by selective PDE4 inhibitors. Amrinone and milrinone, selective PDE3 inhibitors, suppressed TNF secretion to a lesser extent. The effects of theophylline (unspecific PDE inhibitor), vinpocetine (PDE1 inhibitor), EHNA (PDE2 inhibitor) and the PDE5 inhibitors zaprinast and E 4021 were weak. In human blood, the tested glucocorticoids beclomethasone, dexamethasone and fluticasone inhibited the LPS induced TNF release potently in a concentration dependent manner, whereas in dispersed human nasal polyp cells, the effect of the glucocorticoids on allergically induced TNF release, with the exception of dexamethasone, was much less pronounced. Glucocorticoids were the most potent inhibitors of GM-CSF release and the effect correlates well with the affinity to the glucocorticoid receptor. The selective PDE 4 inhibitors, and to a certain extent the PDE3 inhibitors amrinone and milrinone, reduced the GM-CSF release in a concentration dependent manner. In all investigations selective PDE4 inhibitors reduced TNF release to a much higher degree (4-10 fold) than GM-CSF release. PMID:11969359

  12. Immunization with Staphylococcus aureus Clumping Factor B, a Major Determinant in Nasal Carriage, Reduces Nasal Colonization in a Murine Model

    PubMed Central

    Schaffer, Adam C.; Solinga, Robert M.; Cocchiaro, Jordan; Portoles, Marta; Kiser, Kevin B.; Risley, Allison; Randall, Suzanne M.; Valtulina, Viviana; Speziale, Pietro; Walsh, Evelyn; Foster, Timothy; Lee, Jean C.

    2006-01-01

    Staphylococcus aureus is responsible for a wide range of infections, including soft tissue infections and potentially fatal bacteremias. The primary niche for S. aureus in humans is the nares, and nasal carriage is a documented risk factor for staphylococcal infection. Previous studies with rodent models of nasal colonization have implicated capsule and teichoic acid as staphylococcal surface factors that promote colonization. In this study, a mouse model of nasal colonization was utilized to demonstrate that S. aureus mutants that lack clumping factor A, collagen binding protein, fibronectin binding proteins A and B, polysaccharide intercellular adhesin, or the accessory gene regulator colonized as well as wild-type strains colonized. In contrast, mutants deficient in sortase A or clumping factor B (ClfB) showed reduced nasal colonization. Mice immunized intranasally with killed S. aureus cells showed reduced nasal colonization compared with control animals. Likewise, mice that were immunized systemically or intranasally with a recombinant vaccine composed of domain A of ClfB exhibited lower levels of colonization than control animals exhibited. A ClfB monoclonal antibody (MAb) inhibited S. aureus binding to mouse cytokeratin 10. Passive immunization of mice with this MAb resulted in reduced nasal colonization compared with the colonization observed after immunization with an isotype-matched control antibody. The mouse immunization studies demonstrate that ClfB is an attractive component for inclusion in a vaccine to reduce S. aureus nasal colonization in humans, which in turn may diminish the risk of staphylococcal infection. As targets for vaccine development and antimicrobial intervention are assessed, rodent nasal colonization models may be invaluable. PMID:16552044

  13. Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds.

    PubMed

    Shafiee, Abbas; Seyedjafari, Ehsan; Sadat Taherzadeh, Elham; Dinarvand, Peyman; Soleimani, Masoud; Ai, Jafar

    2014-07-01

    Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (l-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors. PMID:24857513

  14. Nasal diagrams: a tool for recording the distribution of nasal lesions in rats and mice.

    PubMed

    Mery, S; Gross, E A; Joyner, D R; Godo, M; Morgan, K T

    1994-01-01

    Knowledge of patterns of lesion distribution can provide insight into the relative roles played by regional tissue dose and local tissue susceptibility in toxic responses to xenobiotics in the nose and assist assessment of potential human risk. A consistent approach is needed for recording lesion distribution patterns in the complex nasal airways of rats and mice. The present work provides a series of diagrams of the nasal passages of the Fischer-344 rat and B6C3F1 mouse, designed for mapping nasal lesions. The diagrams present each of the major cross-sectional airway profiles, provide adequate space for nasal mucosal lesion recording, and are suitable for duplication in a commercial photocopier. Sagittal diagrams are also provided to permit transfer of lesion location data observed in transverse sections onto the long axis of the nose. The distribution of lesions induced by a selected range of xenobiotics is presented. Approaches to application of the diagrams and interpretation of results obtained are discussed in relation to factors responsible for lesion distribution in the nose and their relevance to interspecies extrapolation. A modified approach to anatomical classification of the ethmoturbinates of the rodent is also presented. PMID:7817125

  15. Three Dimension Filamentous Human Cardiac Tissue Model

    PubMed Central

    Ma, Zhen; Koo, Sangmo; Finnegan, Micaela A.; Loskill, Peter; Huebsch, Nathaniel; Marks, Natalie C.; Conklin, Bruce R.; Grigoropoulos, Costas P.; Healy, Kevin E.

    2013-01-01

    A human in vitro cardiac tissue model would be a significant advancement for understanding, studying, and developing new strategies for treating cardiac arrhythmias and related cardiovascular diseases. We developed an in vitro model of three-dimensional (3D) human cardiac tissue by populating synthetic filamentous matrices with cardiomyocytes derived from healthy wild-type volunteer (WT) and patient-specific long QT syndrome type 3 (LQT3) induced pluripotent stem cells (iPS-CMs) to mimic the condensed and aligned human ventricular myocardium. Using such a highly controllable cardiac model, we studied the contractility malfunctions associated with the electrophysiological consequences of LQT3 and their response to a panel of drugs. By varying the stiffness of filamentous matrices, LQT3 iPS-CMs exhibited different level of contractility abnormality and susceptibility to drug-induced cardiotoxicity. PMID:24268663

  16. Effect of High, Medium, and Low Molecular Weight Hyaluronan on Inflammation and Oxidative Stress in an In Vitro Model of Human Nasal Epithelial Cells.

    PubMed

    Albano, Giusy Daniela; Bonanno, Anna; Cavalieri, Luca; Ingrassia, Eleonora; Di Sano, Caterina; Siena, Liboria; Riccobono, Loredana; Gagliardo, Rosalia; Profita, Mirella

    2016-01-01

    IL-17A is involved in the activation of oxidative stress and inflammation in nasal epithelial cells. Hyaluronan (HA) in its high molecular weight form (HMW-HA) shows anti-inflammatory responses in contrast to low and medium molecular weight HA (LMW-HA and MMW-HA). The aim of this study was to investigate the pro- or anti-inflammatory biologic function of HA at different molecular weight in an in vitro model of nasal inflammation IL-17A mediated. We evaluated the ERK1/2 and IκBα phosphorylation, NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 protein, and mRNA levels, in nasal epithelial cells RPMI 2650 stimulated with recombinant human (rh) IL-17A. Furthermore, the cells were treated with HMW-HA, MMW-HA, LMW-HA, and U0126. Our results showed that rhIL-17A increased the ERK1/2, IκBα phosphorylation and NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 proteins, and mRNA levels. The addiction of HMW-HA or U0126 showed a significant downregulatory effect on inflammation due to the rhIL-17A stimulation in nasal epithelial cells. IL-17A is able to generate oxidative stress and inflammation via the activation of ERK1/2/NF-κB pathway in nasal epithelial cells. The HMW-HA might represent a coadjuvant of the classic anti-inflammatory/antioxidative treatment of nasal epithelial cells during IL-17A nasal inflammation. PMID:27212811

  17. Effect of High, Medium, and Low Molecular Weight Hyaluronan on Inflammation and Oxidative Stress in an In Vitro Model of Human Nasal Epithelial Cells

    PubMed Central

    Albano, Giusy Daniela; Bonanno, Anna; Cavalieri, Luca; Ingrassia, Eleonora; Di Sano, Caterina; Siena, Liboria; Riccobono, Loredana; Gagliardo, Rosalia; Profita, Mirella

    2016-01-01

    IL-17A is involved in the activation of oxidative stress and inflammation in nasal epithelial cells. Hyaluronan (HA) in its high molecular weight form (HMW-HA) shows anti-inflammatory responses in contrast to low and medium molecular weight HA (LMW-HA and MMW-HA). The aim of this study was to investigate the pro- or anti-inflammatory biologic function of HA at different molecular weight in an in vitro model of nasal inflammation IL-17A mediated. We evaluated the ERK1/2 and IκBα phosphorylation, NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 protein, and mRNA levels, in nasal epithelial cells RPMI 2650 stimulated with recombinant human (rh) IL-17A. Furthermore, the cells were treated with HMW-HA, MMW-HA, LMW-HA, and U0126. Our results showed that rhIL-17A increased the ERK1/2, IκBα phosphorylation and NF-κB signal pathway activation, ROS production, IL-8 and NOX-4 proteins, and mRNA levels. The addiction of HMW-HA or U0126 showed a significant downregulatory effect on inflammation due to the rhIL-17A stimulation in nasal epithelial cells. IL-17A is able to generate oxidative stress and inflammation via the activation of ERK1/2/NF-κB pathway in nasal epithelial cells. The HMW-HA might represent a coadjuvant of the classic anti-inflammatory/antioxidative treatment of nasal epithelial cells during IL-17A nasal inflammation. PMID:27212811

  18. Frequency domain optical tomography in human tissue

    NASA Astrophysics Data System (ADS)

    Yao, Yuqi; Wang, Yao; Pei, Yaling; Zhu, Wenwu; Hu, Jenhun; Barbour, Randall L.

    1995-10-01

    In this paper, a reconstruction algorithm for frequency-domain optical tomography in human tissue is presented. A fast and efficient multigrid finite difference (MGFD) method is adopted as a forward solver to obtain the simulated detector responses and the required imaging operator. The solutions obtained form MGFD method for 3D problems with weakly discontinuous cocoefficients are compared with analyzed solutions to determine the accuracy of the numerical method. Simultaneous reconstruction of both absorption and scattering coefficients for tissue-like media is accomplished by solving a perturbation equation using the Born approximation. This solution is obtained by a conjugate gradient descent method with Tikhonov regularization. Two examples are given to show the quality of the reconstruction results. Both involve the examination of anatomically accurate optical models of tissue derived from segmented 3D magnetic resonance images to which have been assigned optical coefficients to the designated tissue types. One is a map of a female breast containing two small 'added pathologies', such as tumors. The other is a map of the brain containing a 'local bleeding' area, representing a hemorrhage. The reconstruction results show that the algorithm is computationally practical and can yield qualitatively correct geometry of the objects embedded in the simulated human tissue. Acceptable results are obtaiend even when 10% noise is present in the data.

  19. Effect of nasal decongestion on voice spectrum of a nasal consonant-vowel.

    PubMed

    Lee, Guo-She; Yang, Cheryl C H; Wang, Ching-Ping; Kuo, Terry B J

    2005-03-01

    The nasal cavity and its related structures make significant contributions to human phonation, especially the resonance of voice spectra. The voice spectra of the nasal consonant-vowel (CV), [md:], in the subjects with nasal obstruction were obtained and were compared with the spectra of the same CV vocalized by the same subjects after topical nasal decongestion treatment with 1:1000 epinephrine solution. Results revealed that the intensity damping was more marked in the high-frequency area (>1600 Hz) after the nasal decongestion. Moreover, the intensities of the spectral valleys damped more than the spectral peaks, especially the spectral valley of 1000-2700 Hz. Therefore, a more complex spectral pattern was formed by the resultant uneven damping effect after nasal decongestion. The nasal cavity plays an important role in the formation of spectral peaks and valleys, and such engraved voice spectra may also characterize nasal voices like the nasal CV [md:] demonstrated in our study. PMID:15766851

  20. Three-Dimensional Mapping of Ozone-Induced Injury in the Nasal Airways of Monkeys Using Magnetic Resonance Imaging and Morphometric Techniques

    SciTech Connect

    Carey, Stephen A.; Minard, Kevin R.; Trease, Lynn L.; Wagner, James G.; Garcia, Guilherme M.; Ballinger, Carol A.; Kimbell, Julia; Plopper, Charles G.; Corley, Rick A.; Postlewait, Ed; Harkema, Jack R.

    2007-03-01

    ABSTRACT Age-related changes in gross and microscopic structure of the nasal cavity can alter local tissue susceptibility as well as the dose of inhaled toxicant delivered to susceptible sites. This article describes a novel method for the use of magnetic resonance imaging, 3-dimensional airway modeling, and morphometric techniques to characterize the distribution and magnitude of ozone-induced nasal injury in infant monkeys. Using this method, we are able to generate age-specific, 3-dimensional, epithelial maps of the nasal airways of infant Rhesus macaques. The principal nasal lesions observed in this primate model of ozone-induced nasal toxicology were neutrophilic rhinitis, along with necrosis and exfoliation of the epithelium lining the anterior maxilloturbinate. These lesions, induced by acute or cyclic (episodic) exposures, were examined by light microscopy, quantified by morphometric techniques, and mapped on 3-dimensional models of the nasal airways. Here, we describe the histopathologic, imaging, and computational biology methods developed to efficiently characterize, localize, quantify, and map these nasal lesions. By combining these techniques, the location and severity of the nasal epithelial injury were correlated with epithelial type, nasal airway geometry, and local biochemical and molecular changes on an individual animal basis. These correlations are critical for accurate predictive modeling of exposure-dose-response relationships in the nasal airways, and subsequent extrapolation of nasal findings in animals to humans for developing risk assessment.

  1. Engineering tissue from human embryonic stem cells

    PubMed Central

    Metallo, CM; Azarin, SM; Ji, L; De Pablo, JJ; Palecek, SP

    2008-01-01

    Abstract Recent advances in human embryonic stem cell (hESC) biology now offer an alternative cell source for tissue engineers, as these cells are capable of proliferating indefinitely and differentiating to many clinically relevant cell types. Novel culture methods capable of exerting spatial and temporal control over the stem cell microenvironment allow for more efficient expansion of hESCs, and significant advances have been made toward improving our understanding of the biophysical and biochemical cues that direct stem cell fate choices. Effective production of lineage specific progenitors or terminally differentiated cells enables researchers to incorporate hESC derivatives into engineered tissue constructs. Here, we describe current efforts using hESCs as a cell source for tissue engineering applications, highlighting potential advantages of hESCs over current practices as well as challenges which must be overcome. PMID:18194458

  2. Nasal endoscopy

    MedlinePlus

    ... Search Search MedlinePlus GO GO About MedlinePlus Site Map FAQs Contact Us Health Topics Drugs & Supplements Videos & Tools Español You Are Here: Home → Medical Encyclopedia → Nasal endoscopy URL of this page: //medlineplus.gov/ency/article/ ...

  3. Visual exploration of nasal airflow.

    PubMed

    Zachow, Stefan; Muigg, Philipp; Hildebrandt, Thomas; Doleisch, Helmut; Hege, Hans-Christian

    2009-01-01

    Rhinologists are often faced with the challenge of assessing nasal breathing from a functional point of view to derive effective therapeutic interventions. While the complex nasal anatomy can be revealed by visual inspection and medical imaging, only vague information is available regarding the nasal airflow itself: Rhinomanometry delivers rather unspecific integral information on the pressure gradient as well as on total flow and nasal flow resistance. In this article we demonstrate how the understanding of physiological nasal breathing can be improved by simulating and visually analyzing nasal airflow, based on an anatomically correct model of the upper human respiratory tract. In particular we demonstrate how various Information Visualization (InfoVis) techniques, such as a highly scalable implementation of parallel coordinates, time series visualizations, as well as unstructured grid multi-volume rendering, all integrated within a multiple linked views framework, can be utilized to gain a deeper understanding of nasal breathing. Evaluation is accomplished by visual exploration of spatio-temporal airflow characteristics that include not only information on flow features but also on accompanying quantities such as temperature and humidity. To our knowledge, this is the first in-depth visual exploration of the physiological function of the nose over several simulated breathing cycles under consideration of a complete model of the nasal airways, realistic boundary conditions, and all physically relevant time-varying quantities. PMID:19834215

  4. Alpha-dispersion in human tissue

    NASA Astrophysics Data System (ADS)

    Grimnes, Sverre; Martinsen, Ørjan G.

    2010-04-01

    Beta dispersion is found in living tissue in the kilohertz - megahertz range and is caused by the cellular structure of biological materials with low frequency properties caused by cell membranes. Alpha dispersion is found in the hertz range and the causes are not so well known. Alpha dispersions are the first to disappear when tissue dies. Tissue data have often been based upon excised specimen from animals and are therefore not necessarily representative for human tissue alpha dispersions. Here we present data obtained with non-invasive skin surface electrodes for different segments of the living human body. We found alpha dispersions in all cases; the ankle-wrist results had the smallest. Large alpha dispersions were found where the distance between the electrodes and muscle masses was small, e.g. on the calf. Further studies on electrode technique and reciprocity, electrode positioning, statistical variations, gender, age and bodily constitutions are necessary in order to reveal more about the alpha dispersion, its appearance and disappearance.

  5. Nasal bots...a fascinating world!

    PubMed

    Angulo-Valadez, Carlos E; Scholl, Philip J; Cepeda-Palacios, Ramón; Jacquiet, Philippe; Dorchies, Philippe

    2010-11-24

    Larvae causing obligatory myiasis are numerous and they may affect cutaneous and subcutaneous tissues, wounds, nasopharyngeal cavities (nasal bots), internal organs and the digestive tract (bots) of domestic and wild animals and humans as well. Nasal bots belong to the Family Oestridae, Subfamily Oestrinae, which includes several important genera: Oestrus, Kirkioestrus, and Gedoelstia infecting Artiodactyla (except Cervidae) in Africa and Eurasia, Cephenemyia and Pharyngomyia infecting Cervidae, Rhinoestrus infecting horses, Cephalopina infecting camels, Pharyngobolus infecting African elephants, and Tracheomyia infecting Australian kangaroos. Nasal bots are widespread in Mediterranean and tropical areas and in affected animals they induce sneezing and nasal discharge which may become caked with dust making breathing very difficult. The aforementioned species of larvae are host-specific but sometimes the may be deposited in human eyes inducing a painful opthalmomyiasis of short duration. The first fascinating trait of these parasites is the very efficient morphological and biological adaptations to parasitism they show either as larvae or as adults, in order to facilitate their survival and search for a suitable host. Nasal bots have reached different degrees of complexity in their life cycles. Indeed, while for some species (e.g., Oestrus ovis, Rhinoestrus usbekistanicus) larvae are injected by flies directly into nostrils and develop in the sinuses before being ejected for external pupation, some other species migrate from eyes to blood before returning to nasal cavities either through the ethmoid bone (Gedoelstia hässleri) or via lungs and bronchi (Gedoelstia cristata). Moreover, larvae are very well-adapted to their environment being able to undergo through hypobiosis either inside or outside the host, according to the climatic environmental conditions and seasonality. The second fascinating trait of nasal bots is related to host behavioural and immune

  6. Depicting the inner and outer nose: the representation of the nose and the nasal mucosa on the human primary somatosensory cortex (SI).

    PubMed

    Gastl, Mareike; Brünner, Yvonne F; Wiesmann, Martin; Freiherr, Jessica

    2014-09-01

    The nose is important not only for breathing, filtering air, and perceiving olfactory stimuli. Although the face and hands have been mapped, the representation of the internal and external surface of the nose on the primary somatosensory cortex (SI) is still poorly understood. To fill this gap functional magnetic resonance imaging (fMRI) was used to localize the nose and the nasal mucosa in the Brodman areas (BAs) 3b, 1, and 2 of the human postcentral gyrus (PG). Tactile stimulation during fMRI was applied via a customized pneumatically driven device to six stimulation sites: the alar wing of the nose, the lateral nasal mucosa, and the hand (serving as a reference area) on the left and right side of the body. Individual representations could be discriminated for the left and right hand, for the left nasal mucosa and left alar wing of the nose in BA 3b and BA 1 by comparing mean activation maxima and Euclidean distances. Right-sided nasal conditions and conditions in BA 2 could further be separated by different Euclidean distances. Regarding the alar wing of the nose, the results concurred with the classic sensory homunculus proposed by Penfield and colleagues. The nasal mucosa was not only determined an individual and bilateral representation, its position on the somatosensory cortex is also situated closer to the caudal end of the PG compared to that of the alar wing of the nose and the hand. As SI is commonly activated during the perception of odors, these findings underscore the importance of the knowledge of the representation of the nasal mucosa on the primary somatosensory cortex, especially for interpretation of results of functional imaging studies about the sense of smell. PMID:24659451

  7. Sorption studies of human keratinized tissues

    NASA Astrophysics Data System (ADS)

    Johnsen, G. K.; Martinsen, Ø. G.; Grimnes, Sverre

    2010-04-01

    Water content is known to be the most important single parameter for keratinized tissue to remain its vital functions. In that sense, a general knowledge of the water binding properties is of great interest, and a reliable measurement setup must be found. Also, revealing the sorption properties of human keratinized tissues is vital towards a calibration of susceptance based skin hydration measurements that already is an important diagnostic tool in clinical dermatology, and we will see that any hysteresis will complicate such a calibration further. In this study we investigated the sorption properties of keratinized tissues such as human epidermal stratum corneum (SC), hair and nail. The study was performed under controlled environmental conditions with a dynamic vapor sorption (DVS) instrument, and the water uptake of the keratinized test samples was measured as the relative humidity in the ambient air was altered step-wisely. In this study, vital and characteristic water sorption properties such as the isotherm, relative water uptake, and hysteresis were investigated and will be discussed.

  8. Finite Element Modeling of Human Placental Tissue

    PubMed Central

    Yu, Mao; Manoogian, Sarah; Duma, Stefan M.; Stitzel, Joel D.

    2009-01-01

    Motor vehicle crashes account for a large portion of placental abruption and fetal losses. To better understand the material properties of the human placenta, a Finite Element (FE) model of human placenta tissue was created and verified using data from uniaxial tension tests. Sixty-four tensile tests at three different strain rates of 7% strain/s, 70% strain/s, and 700% strain/s from six whole human placentas were used for model development. Nominal stresses were calculated by dividing forces at the grips by the original cross-sectional area. Nominal strains were calculated by dividing cross-head displacement by the original gauge length. A detailed methodology for interpreting experimental data for application to material model development is presented. A model of the tension coupon was created in LS-DYNA and stretched in the same manner as the uniaxial tension tests. The behavior of the material was optimized to the uniaxial tension test using a multi-island genetic algorithm. The results demonstrate good correlation between experiments and the model, with an average difference of 2% between the optimized FE and experimental first principal stress at the termination state. The material parameters found in this study can be utilized in FE models of placental tissues for behavior under dynamic loading. PMID:20184849

  9. Verruculogen associated with Aspergillus fumigatus hyphae and conidia modifies the electrophysiological properties of human nasal epithelial cells

    PubMed Central

    Khoufache, Khaled; Puel, Olivier; Loiseau, Nicolas; Delaforge, Marcel; Rivollet, Danièle; Coste, André; Cordonnier, Catherine; Escudier, Estelle; Botterel, Françoise; Bretagne, Stéphane

    2007-01-01

    Background The role of Aspergillus fumigatus mycotoxins in the colonization of the respiratory tract by conidia has not been studied extensively, even though patients at risk from invasive aspergillosis frequently exhibit respiratory epithelium damage. In a previous study, we found that filtrates of A. fumigatus cultures can specifically alter the electrophysiological properties of human nasal epithelial cells (HNEC) compared to those of non pathogenic moulds. Results We fractionated the organic phase of filtrate from 3-day old A. fumigatus cultures using high-performance liquid chromatography. The different fractions were tested for their ability to modify the electrophysiological properties of HNEC in an in vitro primary culture model. The fraction collected between 20 and 30 min mimicked the effects of the whole filtrate, i.e. decrease of transepithelial resistance and increase of potential differences, and contained secondary metabolites such as helvolic acid, fumagillin, and verruculogen. Only verruculogen (10-8 M) had effects similar to the whole filtrate. We verified that verruculogen was produced by a collection of 67 human, animal, plant and environmental A. fumigatus isolates. Using MS-MS analysis, we found that verruculogen was associated with both mycelium and conidia extracts. Conclusion Verruculogen is a secondary metabolite that modifies the electrophysiological properties of HNEC. The role of these modifications in the colonization and invasion of the respiratory epithelium by A. fumigatus on first contact with the epithelium remains to be determined. PMID:17244350

  10. The Effect of Menstrual Cycle on Nasal Resonance Characteristics in Females

    ERIC Educational Resources Information Center

    Kumar, Suman; Basu, Shriya; Sinha, Anisha; Chatterjee, Indranil

    2012-01-01

    The purpose of this study was to analyze resonance characteristics (nasality and nasalance values) during the menstrual cycle. Previous studies indicate changes in voice quality and nasal mucosa due to temporary falling estrogen levels in human females during their menstrual cycle. The present study compared the nasality and "nasalance scores"…

  11. Beclomethasone Nasal Spray

    MedlinePlus

    ... relieve symptoms of sneezing, runny, stuffy, or itchy nose (rhinitis) caused by hay fever, other allergies, or ... nasal polyps (swelling of the lining of the nose) after nasal polyp removal surgery. Beclomethasone nasal spray ...

  12. Hippocampus and epilepsy: Findings from human tissues.

    PubMed

    Huberfeld, G; Blauwblomme, T; Miles, R

    2015-03-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several focal epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including temporal lobe epilepsies with hippocampal sclerosis, cortical dysplasias, epilepsies associated with tumors and developmental malformations. Slices of tissue from patients with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in the neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum, an output region, which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells, which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide restores intracellular chloride and thus hyperpolarizing GABAergic actions and consequently suppressing interictal

  13. Hippocampus and epilepsy: findings from human tissues

    PubMed Central

    Huberfeld, Gilles; Blauwblomme, Thomas; Miles, Richard

    2015-01-01

    Surgical removal of the epileptogenic zone provides an effective therapy for several epileptic syndromes. This surgery offers the opportunity to study pathological activity in living human tissue for pharmacoresistant partial epilepsy syndromes including (1) temporal lobe epilepsies with hippocampal sclerosis, (2) cortical dysplasias, (3) epilepsies associated with tumors and (4) developmental malformations. Slices of tissue from patient with these syndromes retain functional neuronal networks and may generate epileptic activities. The properties of cells in this tissue may not be greatly changed, but excitatory synaptic transmission is often enhanced and GABAergic inhibition is preserved. Typically epileptic activity is not generated spontaneously by the neocortex, whether dysplastic or not, but can be induced by convulsants. The initiation of ictal discharges in neocortex depends on both GABAergic signaling and increased extracellular potassium. In contrast, a spontaneous interictal-like activity is generated by tissues from patients with temporal lobe epilepsies associated with hippocampal sclerosis. This activity is initiated, not in the hippocampus but in the subiculum an output region which projects to the entorhinal cortex. Interictal events seem to be triggered by GABAergic cells which paradoxically excite about 20% of subicular pyramidal cells while simultaneously inhibiting the majority. Interictal discharges thus depend on both GABAergic and glutamatergic signaling. The depolarizing effects of GABA depend on a pathological elevation in levels of chloride in some subicular cells, similar to those of developmentally immature cells. Such defect is caused by a perturbed expression of the cotransporters regulating intracellular chloride concentration, the importer NKCC1 and the extruder KCC2. Blockade of NKCC1 actions by the diuretic bumetanide, restores intracellular chloride and thus hyperpolarizing GABAergic actions so suppressing interictal activity. PMID

  14. Live attenuated influenza vaccine strains elicit a greater innate immune response than antigenically-matched seasonal influenza viruses during infection of human nasal epithelial cell cultures.

    PubMed

    Fischer, William A; Chason, Kelly D; Brighton, Missy; Jaspers, Ilona

    2014-03-26

    Influenza viruses are global pathogens that infect approximately 10-20% of the world's population each year. Vaccines, including the live attenuated influenza vaccine (LAIV), are the best defense against influenza infections. The LAIV is a novel vaccine that actively replicates in the human nasal epithelium and elicits both mucosal and systemic protective immune responses. The differences in replication and innate immune responses following infection of human nasal epithelium with influenza seasonal wild type (WT) and LAIV viruses remain unknown. Using a model of primary differentiated human nasal epithelial cell (hNECs) cultures, we compared influenza WT and antigenically-matched cold adapted (CA) LAIV virus replication and the subsequent innate immune response including host cellular pattern recognition protein expression, host innate immune gene expression, secreted pro-inflammatory cytokine production, and intracellular viral RNA levels. Growth curves comparing virus replication between WT and LAIV strains revealed significantly less infectious virus production during LAIV compared with WT infection. Despite this disparity in infectious virus production the LAIV strains elicited a more robust innate immune response with increased expression of RIG-I, TLR-3, IFNβ, STAT-1, IRF-7, MxA, and IP-10. There were no differences in cytotoxicity between hNEC cultures infected with WT and LAIV strains as measured by basolateral levels of LDH. Elevated levels of intracellular viral RNA during LAIV as compared with WT virus infection of hNEC cultures at 33°C may explain the augmented innate immune response via the up-regulation of pattern recognition receptors and down-stream type I IFN expression. Taken together our results suggest that the decreased replication of LAIV strains in human nasal epithelial cells is associated with a robust innate immune response that differs from infection with seasonal influenza viruses, limits LAIV shedding and plays a role in the silent

  15. [Arteriovenous anastomosis in nasal cavities using microcorrosion technique].

    PubMed

    Passàli, D; Buccella, M G; Vetuschi, A; Bellussi, L

    1990-01-01

    In the present study the morphology of arteriovenous anastomoses in the nasal area are analyzed using the microcorrosion technique. This technique calls for perfusion of the vascular system, passing through the left ventricle, with Batson's of the vessels. For the first time in the microcorrosion study of the nasal vascular network human fetuses (from the 12th to 24th week of intrauterine life) obtained from spontaneous abortions were used as well as rats weighing from 250 to 300 gr. The animals were anesthetized with sodium thiopental prior to administration of the resin. A specimen containing the facial muscles, the nasal pyramid, the maxillary bone and the palatine bones was excised. Then, from this specimen the nasal septum and the two lateral portions of the nose were obtained. The bony and soft perivascular tissues were removed by placing the casts in an aqueous 20% KOH solution. Finally the corrosion cases were observed under a scanning electron microscope (EM). Within the nasal cavities the microcorrosion technique makes it possible to identify three different vascular layers: superficial, intermediate and deep. In the latter it proved possible to visualize the two types of arteriovenous anastomoses: i.e. simple and complex. On the basis of both vascular course and the impressions left by the endothelial cell nuclei it proved possible to differentiate between the arterial and venous portions of the anastomoses. PMID:2095105

  16. Nasal ventilation.

    PubMed Central

    Simonds, A. K.

    1998-01-01

    Nasal intermittent positive pressure ventilation is likely to have an increasing role in the management of acute ventilatory failure, weaning, and chronic ventilatory problems. Further improvements in ventilator and mask design will be seen. Appropriate application is likely to reduce both mortality and admissions to intensive care, while domiciliary use can improve life expectancy and/or quality of life in chronic ventilatory disorders. As with any new technique, enthusiasm should not outweigh clear outcome information, and possible new indications should always be subject to careful assessment. Images Figure 2 PMID:9799887

  17. Merizocotyle euzeti sp. n. (Monogenea: Monocotylidae) from the nasal tissue of three deep sea skates (Rajidae) in the southwestern Atlantic Ocean.

    PubMed

    Irigoitia, Manuel M; Cantatore, Delfina M P; Delpiani, Gabriela E; Incorvaia, Inés S; Lanfranchi, Ana L; Timi, Juan T

    2014-06-01

    A new species of Merizocotyle Cerfontaine, 1894 (Monogenea: Monocotylidae) is described from the nasal tissues of three deep sea rajid skates: the southern thorny skate, Amblyraja doellojuradoi (Pozzi), broadnose skate, Bathyraja brachyurops (Fowler), and yellownose skate, Zearaja chilensis (Guichenot), collected off Buenos Aires Province, Argentina, southwest Atlantic Ocean. Two additional species of sympatric rajid, the white-dotted skate, Bathyraja albomaculata (Norman), and the Patagonian skate, Bathyraja macloviana (Norman), were also examined but no merizocotylines were found. The taxonomy of the Merizocotylinae is not widely accepted and, as a result, the status of Thaumatocotyle and Mycteronastes, and their proposed synonymy with Merizocotyle are currently under discussion. The new species differs from its congeners by having a unique haptoral structure, 6 peripheral loculi that are asymmetrically arranged (one much smaller, indistinctly located in the left or right side of the haptor). The presence of the new species in three sympatric species of Rajidae belonging to distinct genera and subfamilies, as well as its absence in sympatric congenerics indicates the lack of phylogenetic host specificity. Host ecology and geographical distribution appear to be more important than host phylogeny in determining the distribution of this parasite across potential hosts in the region. This constitutes the first record of Merizocotyle in the southwestern Atlantic Ocean. PMID:25065126

  18. Glycoconjugate expression in follicle-associated epithelium (FAE) covering the nasal-associated lymphoid tissue (NALT) in specific pathogen-free and conventional rats.

    PubMed

    Jeong, K I; Uetsuka, K; Nakayama, H; Doi, K

    1999-01-01

    We examined lectin-histochemically the glycoconjugate expression in the follicle-associated epithelium (FAE) covering the nasal-associated lymphoid tissue (NALT) in the rat under specific pathogen-free (SPF) and conventional (CV) conditions and compared the results for SPF and CV rats as well as for membranous (M) cells and adjacent ciliated respiratory epithelial (CRE) cells in FAE. N-acetylgalactosamine-specific lectins, Dolichos biflorus (DBA), Helix pomatia (HPA), Glycine max (SBA) and Vicia villosa (VVA), and alpha-L-fucose-specific lectin, Ulex europaeus (UEA-I), preferentially bound to M cells mainly in the luminal surface compared with CRE cells in SPF rats, whereas DBA and UEA-I showed signs of preferential binding to the apical and basolateral cytoplasm as well as to the luminal surface of M cells in CV rats. In addition, HPA, SBA and VVA more frequently and extensively labeled M cells than CRE cells in CV rats with the same subcellular staining pattern as DBA and UEA-I. On the whole, the changes in lectin binding frequency and strength were more prominent in M cells than in CRE cells in both SPF and CV rats. The present results indicate that DBA and UEA-I are useful as markers of M cells in NALT. Furthermore, the pattern of expression of carbohydrate residues recognized by such lectins in SPF and CV rats suggests that M cells are highly sensitive to environmental changes. PMID:10067202

  19. Nasal septal ulceration.

    PubMed

    Sardana, Kabir; Goel, Khushbu

    2014-01-01

    Nasal septal ulceration can have multiple etiologies. Determining the exact cause depends on who the consulting specialist is, who could either be the ENT surgeon or the dermatologist. The common causes are infections (tuberculosis, leprosy, leishmaniasis), vasculitis (Wegener's granulomatosis and Churg-Strauss syndrome), and lupus erythematosus. Traumatic causes and malignancy can also be seen in tertiary referral centers. The diagnosis often requires thorough investigations and multiple tissue specimens from various sites, and in chronic cases, a suspicion of lymphoma should be considered. Apart from disease-specific therapy, a multidisciplinary approach is required in most cases to tackle the cosmetic disfigurement. PMID:25441476

  20. Proteomics. Tissue-based map of the human proteome.

    PubMed

    Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M; Lindskog, Cecilia; Oksvold, Per; Mardinoglu, Adil; Sivertsson, Åsa; Kampf, Caroline; Sjöstedt, Evelina; Asplund, Anna; Olsson, IngMarie; Edlund, Karolina; Lundberg, Emma; Navani, Sanjay; Szigyarto, Cristina Al-Khalili; Odeberg, Jacob; Djureinovic, Dijana; Takanen, Jenny Ottosson; Hober, Sophia; Alm, Tove; Edqvist, Per-Henrik; Berling, Holger; Tegel, Hanna; Mulder, Jan; Rockberg, Johan; Nilsson, Peter; Schwenk, Jochen M; Hamsten, Marica; von Feilitzen, Kalle; Forsberg, Mattias; Persson, Lukas; Johansson, Fredric; Zwahlen, Martin; von Heijne, Gunnar; Nielsen, Jens; Pontén, Fredrik

    2015-01-23

    Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. PMID:25613900

  1. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  2. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  3. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  4. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  5. 21 CFR 1270.42 - Human tissue offered for import.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Human tissue offered for import. 1270.42 Section 1270.42 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) REGULATIONS UNDER CERTAIN OTHER ACTS ADMINISTERED BY THE FOOD AND DRUG ADMINISTRATION HUMAN TISSUE...

  6. A Controlled Challenge Study on Di(2-ethylhexyl) Phthalate (DEHP) in House Dust and the Immune Response in Human Nasal Mucosa of Allergic Subjects

    PubMed Central

    Deutschle, Tom; Reiter, Rudolf; Butte, Werner; Heinzow, Birger; Keck, Tilman; Riechelmann, Herbert

    2008-01-01

    Background Few studies have yet addressed the effects of di(2-ethylhexyl) phthalate (DEHP) in house dust on human nasal mucosa. Objectives We investigated the effects of house dust containing DEHP on nasal mucosa of healthy and house dust mite (HDM)–allergic subjects in a short-term exposure setting. Methods We challenged 16 healthy and 16 HDM-allergic subjects for 3 hr with house dust at a concentration of 300 μg/m3 containing either low (0.41 mg/g) or high (2.09 mg/g) levels of DEHP. Exposure to filtered air served as control. After exposure, we measured proteins and performed a DNA microarray analysis. Results Nasal exposure to house dust with low or high DEHP had no effect on symptom scores. Healthy subjects had almost no response to inhaled dust, but HDM-allergic subjects showed varied responses: DEHPlow house dust increased eosinophil cationic protein, granulocyte-colony–stimulating factor (G-CSF), interleukin (IL)-5, and IL-6, whereas DEHPhigh house dust decreased G-CSF and IL-6. Furthermore, in healthy subjects, DEHP concentration resulted in 10 differentially expressed genes, whereas 16 genes were differentially expressed in HDM-allergic subjects, among them anti-Müllerian hormone, which was significantly up-regulated after exposure to DEHPhigh house dust compared with exposure to DEHPlow house dust, and fibroblast growth factor 9, IL-6, and transforming growth factor-β1, which were down-regulated. Conclusions Short-term exposure to house dust with high concentrations of DEHP has attenuating effects on human nasal immune response in HDM-allergic subjects, concerning both gene expression and cytokines. PMID:19057701

  7. Imaging the Human Body: Micro- and Nanostructure of Human Tissues

    NASA Astrophysics Data System (ADS)

    Schulz, Georg; Deyhle, Hans; Müller, Bert

    Computed tomography based on X-rays is known to provide the best spatial resolution of all clinical three-dimensional imaging facilities and currently reaches a fraction of a millimeter. Better spatial and density resolution is obtained by means of micro computed tomography well established in the field of materials science. It is also very supportive imaging human tissues down to the level of individual cells (Lareida et al. J. Microsc. 234:95, 2009). The article demonstrates the power of micro computed tomography for imaging parts of the human body such as teeth, inner ear, cerebellum, tumors, and urethral tissue with conventional X-ray sources and synchrotron radiation facilities in absorption and phase contrast modes. The second part of the chapter relies on scanning X-ray scattering of tooth slices (Müller et al. Eur. J. Clin. Nanomed. 3:30, 2010) to uncover the presence of nanostructures including their anisotropy and orientation. This imaging technique gives unrivalled insights for medical experts, which will have a major influence on fields such as dental and incontinence treatments.

  8. In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells.

    PubMed

    Jukosky, James; Gosselin, Benoit J; Foley, Leah; Dechen, Tenzin; Fiering, Steven; Crane-Godreau, Mardi A

    2015-01-01

    Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual's susceptibility to pathogen infection. PMID:26793127

  9. In vivo Cigarette Smoke Exposure Decreases CCL20, SLPI, and BD-1 Secretion by Human Primary Nasal Epithelial Cells

    PubMed Central

    Jukosky, James; Gosselin, Benoit J.; Foley, Leah; Dechen, Tenzin; Fiering, Steven; Crane-Godreau, Mardi A.

    2016-01-01

    Smokers and individuals exposed to second-hand cigarette smoke have a higher risk of developing chronic sinus and bronchial infections. This suggests that cigarette smoke (CS) has adverse effects on immune defenses against pathogens. Epithelial cells are important in airway innate immunity and are the first line of defense against infection. Airway epithelial cells not only form a physical barrier but also respond to the presence of microbes by secreting antimicrobials, cytokines, and chemokines. These molecules can lyse infectious microorganisms and/or provide signals critical to the initiation of adaptive immune responses. We examined the effects of CS on antimicrobial secretions of primary human nasal epithelial cells (PHNECs). Compared to non-CS-exposed individuals, PHNEC from in vivo CS-exposed individuals secreted less chemokine ligand (C-C motif) 20 (CCL20), Beta-defensin 1 (BD-1), and SLPI apically, less BD-1 and SLPI basolaterally, and more CCL20 basolaterally. Cigarette smoke extract (CSE) exposure in vitro decreased the apical secretion of CCL20 and beta-defensin 1 by PHNEC from non-CS-exposed individuals. Exposing PHNEC from non-CS exposed to CSE also significantly decreased the levels of many mRNA transcripts that are involved in immune signaling. Our results show that in vivo or in vitro exposure to CS alters the secretion of key antimicrobial peptides from PHNEC, but that in vivo CS exposure is a much more important modifier of antimicrobial peptide secretion. Based on the gene expression data, it appears that CSE disrupts multiple immune signaling pathways in PHNEC. Our results provide mechanistic insight into how CS exposure alters the innate immune response and increases an individual’s susceptibility to pathogen infection. PMID:26793127

  10. Gene Electrotransfer in 3D Reconstructed Human Dermal Tissue.

    PubMed

    Madi, Moinecha; Rols, Marie-Pierre; Gibot, Laure

    2016-01-01

    Gene electrotransfer into the skin is of particular interest for the development of medical applications including DNA vaccination, cancer treatment, wound healing or treatment of local skin disorders. However, such clinical applications are currently limited due to poor understanding of the mechanisms governing DNA electrotransfer within human tissue. Nowadays, most studies are carried out in rodent models but rodent skin varies from human skin in terms of cell composition and architecture. We used a tissue-engineering approach to study gene electrotransfer mechanisms in a human tissue context. Primary human dermal fibroblasts were cultured according to the self-assembly method to produce 3D reconstructed human dermal tissue. In this study, we showed that cells of the reconstructed cutaneous tissue were efficiently electropermeabilized by applying millisecond electric pulses, without affecting their viability. A reporter gene was successfully electrotransferred into this human tissue and gene expression was detected for up to 48h. Interestingly, the transfected cells were solely located on the upper surface of the tissue, where they were in close contact with plasmid DNA solution. Furthermore, we report evidences that electrotransfection success depends on plasmid mobility within tissue- rich in collagens, but not on cell proliferation status. In conclusion, in addition to proposing a reliable alternative to animal experiments, tissue engineering produces valid biological tool for the in vitro study of gene electrotransfer mechanisms in human tissue. PMID:27029947

  11. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques.

    PubMed

    Fukuyama, Y; Yuki, Y; Katakai, Y; Harada, N; Takahashi, H; Takeda, S; Mejima, M; Joo, S; Kurokawa, S; Sawada, S; Shibata, H; Park, E J; Fujihashi, K; Briles, D E; Yasutomi, Y; Tsukada, H; Akiyoshi, K; Kiyono, H

    2015-09-01

    We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [(18)F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [(18)F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans. PMID:25669148

  12. Nanogel-based pneumococcal surface protein A nasal vaccine induces microRNA-associated Th17 cell responses with neutralizing antibodies against Streptococcus pneumoniae in macaques

    PubMed Central

    Fukuyama, Y; Yuki, Y; Katakai, Y; Harada, N; Takahashi, H; Takeda, S; Mejima, M; Joo, S; Kurokawa, S; Sawada, S; Shibata, H; Park, E J; Fujihashi, K; Briles, D E; Yasutomi, Y; Tsukada, H; Akiyoshi, K; Kiyono, H

    2015-01-01

    We previously established a nanosized nasal vaccine delivery system by using a cationic cholesteryl group-bearing pullulan nanogel (cCHP nanogel), which is a universal protein-based antigen-delivery vehicle for adjuvant-free nasal vaccination. In the present study, we examined the central nervous system safety and efficacy of nasal vaccination with our developed cCHP nanogel containing pneumococcal surface protein A (PspA-nanogel) against pneumococcal infection in nonhuman primates. When [18F]-labeled PspA-nanogel was nasally administered to a rhesus macaque (Macaca mulatta), longer-term retention of PspA was noted in the nasal cavity when compared with administration of PspA alone. Of importance, no deposition of [18F]-PspA was seen in the olfactory bulbs or brain. Nasal PspA-nanogel vaccination effectively induced PspA-specific serum IgG with protective activity and mucosal secretory IgA (SIgA) Ab responses in cynomolgus macaques (Macaca fascicularis). Nasal PspA-nanogel-induced immune responses were mediated through T-helper (Th) 2 and Th17 cytokine responses concomitantly with marked increases in the levels of miR-181a and miR-326 in the serum and respiratory tract tissues, respectively, of the macaques. These results demonstrate that nasal PspA-nanogel vaccination is a safe and effective strategy for the development of a nasal vaccine for the prevention of pneumonia in humans. PMID:25669148

  13. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  14. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  15. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  16. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  17. 21 CFR 874.3900 - Nasal dilator.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Nasal dilator. 874.3900 Section 874.3900 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES EAR, NOSE, AND THROAT DEVICES Prosthetic Devices § 874.3900 Nasal dilator. (a) Identification. A...

  18. Morphogenesis of respiratory syncytial virus in human primary nasal ciliated epithelial cells occurs at surface membrane microdomains that are distinct from cilia

    SciTech Connect

    Jumat, Muhammad Raihan; Yan, Yan; Ravi, Laxmi Iyer; Wong, Puisan; Huong, Tra Nguyen; Li, Chunwei; Tan, Boon Huan; Wang, De Yun; Sugrue, Richard J.

    2015-10-15

    The distribution of cilia and the respiratory syncytial virus (RSV) nucleocapsid (N) protein, fusion (F) protein, attachment (G) protein, and M2-1 protein in human ciliated nasal epithelial cells was examined at between 1 and 5 days post-infection (dpi). All virus structural proteins were localized at cell surface projections that were distinct from cilia. The F protein was also trafficked into the cilia, and while its presence increased as the infection proceeded, the N protein was not detected in the cilia at any time of infection. The presence of the F protein in the cilia correlated with cellular changes in the cilia and reduced cilia function. At 5 dpi extensive cilia loss and further reduced cilia function was noted. These data suggested that although RSV morphogenesis occurs at non-cilia locations on ciliated nasal epithelial cells, RSV infection induces changes in the cilia body that leads to extensive cilia loss. - Highlights: • Respiratory syncytial virus (RSV) infects nasal ciliated epithelial cells. • Virus morphogenesis occurs within filamentous projections distinct from cilia. • The RSV N protein was not detected in the cilia at any time during infection. • Trafficking of the F protein into the cilia occurred early in infection. • Presence of the F protein in cilia correlated with impaired cilia function.

  19. VR-based interactive CFD data comparison of flow fields in a human nasal cavity

    NASA Astrophysics Data System (ADS)

    Gerndt, Andreas; Kuhlen, Torsten; van Reimersdahl, Thomas; Haack, Matthias; Bischof, Christian

    2004-05-01

    The Virtual Reality Center Aachen is developing a Virtual Reality based operation planning system in cooperation with aerodynamics scientists and physicians of several clinical centers. This system is meant to help the preparation of nose surgeries aimed at the elimination of respiratory diseases. A core part is the interactive comparison of experimental data and simulation data in the area of fluid dynamics. In a first step, data comparison is to depict the differences between healthy noses and diseased noses. Later on, data comparison should supply evidence for successful virtual surgeries, which finally results in guidance on the real operation. During virtual surgery sessions, scientists can interactively explore, analyze, annotate, and compare various medical and aerodynamics data sets. Image-based methods are used to extract several features in one image and between compared data sets. The determination of linked features between different data sets is a particular challenge because of their different time frames, scales, and distortions. An optimized human computer interface enables the user to interact intuitively within a virtual environment in order to select and deal with these data sets. Additionally to this interactive exploration, the system also allows automatic searches for cut plane and key frame candidates corresponding to given feature patterns. The comparison system makes use of an already implemented parallelized Computational Fluid Dynamics (CFD) postprocessing, which also extracts enhanced flow features that allow automatic detection of relevant flow regions. Beside vortex detection, the computation of critical points including flow field segmentation is a current research activity. These flow features are favored characteristics for the comparison and help considerably to classify different nose geometries and operation recommendations.

  20. Validation of excised bovine nasal mucosa as in vitro model to study drug transport and metabolic pathways in nasal epithelium.

    PubMed

    Schmidt, M C; Simmen, D; Hilbe, M; Boderke, P; Ditzinger, G; Sandow, J; Lang, S; Rubas, W; Merkle, H P

    2000-03-01

    The present work aims at the validation of excised bovine nasal mucosa as an in vitro model to address transport and metabolism pathways relative to the nasal mucosal uptake of therapeutic peptides. Preservation of the viability of the excised tissue in the course of in vitro studies of up to 3 h was demonstrated by (i) positive viability staining, (ii) constant transepithelial electrical resistance (42 +/- 12 Omega cm(2)), (iii) constant rates of metabolic turnover, and (iv) linear permeation profiles of therapeutic peptides and (3)H-mannitol. Using 1-leucine-4-methoxy-2-naphthylamide as a model substrate, we observed no difference between bovine and human nasal aminopeptidase activity. By a series of therapeutic peptides, no direct correlation was found between their effective permeability coefficients (from 0. 1 x 10(-5) to 5 x 10(-5) cm s(-1)) and their respective molecular masses (from 417 to 3,432 Da), indicating that other factors dominate nasal permeability. For instance, the permeabilities of metabolically labile peptides were concentration dependent and saturable, as demonstrated for two short thymopoietin fragments, Arg-Lys-Asp (TP3) and Arg-Lys-Asp-Val (TP4). By permeation studies using gonadorelin and two gonadorelin derivatives, buserelin and Hoe 013, without and in the presence of the chemical enhancer bacitracin, we also verified the ability of the model to assess chemical enhancer effects and their reversibility. In conclusion, our work demonstrates the potential of the investigated in vitro model, excised bovine nasal mucosa, to explore mechanistic aspects of nasal transport and metabolism of therapeutic peptides. PMID:10707019

  1. Seeded Amplification of Chronic Wasting Disease Prions in Nasal Brushings and Recto-anal Mucosa-Associated Lymphoid Tissues from Elk by Real-Time Quaking-Induced Conversion.

    PubMed

    Haley, Nicholas J; Siepker, Chris; Hoon-Hanks, Laura L; Mitchell, Gordon; Walter, W David; Manca, Matteo; Monello, Ryan J; Powers, Jenny G; Wild, Margaret A; Hoover, Edward A; Caughey, Byron; Richt, Jürgen A

    2016-04-01

    Chronic wasting disease (CWD), a transmissible spongiform encephalopathy of cervids, was first documented nearly 50 years ago in Colorado and Wyoming and has since been detected across North America and the Republic of Korea. The expansion of this disease makes the development of sensitive diagnostic assays and antemortem sampling techniques crucial for the mitigation of its spread; this is especially true in cases of relocation/reintroduction or prevalence studies of large or protected herds, where depopulation may be contraindicated. This study evaluated the sensitivity of the real-time quaking-induced conversion (RT-QuIC) assay of recto-anal mucosa-associated lymphoid tissue (RAMALT) biopsy specimens and nasal brushings collected antemortem. These findings were compared to results of immunohistochemistry (IHC) analysis of ante- and postmortem samples. RAMALT samples were collected from populations of farmed and free-ranging Rocky Mountain elk (Cervus elaphus nelsoni;n= 323), and nasal brush samples were collected from a subpopulation of these animals (n= 205). We hypothesized that the sensitivity of RT-QuIC would be comparable to that of IHC analysis of RAMALT and would correspond to that of IHC analysis of postmortem tissues. We found RAMALT sensitivity (77.3%) to be highly correlative between RT-QuIC and IHC analysis. Sensitivity was lower when testing nasal brushings (34%), though both RAMALT and nasal brush test sensitivities were dependent on both thePRNPgenotype and disease progression determined by the obex score. These data suggest that RT-QuIC, like IHC analysis, is a relatively sensitive assay for detection of CWD prions in RAMALT biopsy specimens and, with further investigation, has potential for large-scale and rapid automated testing of antemortem samples for CWD. PMID:26888899

  2. Transplantation of a tissue-engineered human vascularized cardiac muscle.

    PubMed

    Lesman, Ayelet; Habib, Manhal; Caspi, Oren; Gepstein, Amira; Arbel, Gil; Levenberg, Shulamit; Gepstein, Lior

    2010-01-01

    Myocardial regeneration strategies have been hampered by the lack of sources for human cardiomyocytes (CMs) and by the significant donor cell loss following transplantation. We assessed the ability of a three-dimensional tissue-engineered human vascularized cardiac muscle to engraft in the in vivo rat heart and to promote functional vascularization. Human embryonic stem cell-derived CMs alone or with human endothelial cells (human umbilical vein endothelial cells) and embryonic fibroblasts (triculture constructs) were seeded onto biodegradable porous scaffolds. The resulting tissue constructs were transplanted to the in vivo rat heart and formed cardiac tissue grafts. Immunostaining studies for human-specific CD31 and alpha-smooth muscle actin demonstrated the formation of both donor (human) and host (rat)-derived vasculature within the engrafted triculture tissue constructs. Intraventricular injection of fluorescent microspheres or lectin resulted in their incorporation by human-derived vessels, confirming their functional integration with host coronary vasculature. Finally, the number of blood vessels was significantly greater in the triculture tissue constructs (60.3 +/- 8/mm(3), p < 0.05) when compared with scaffolds containing only CMs (39.0 +/- 14.4/mm(3)). In conclusion, a tissue-engineered human vascularized cardiac muscle can be established ex vivo and transplanted in vivo to form stable grafts. By utilizing a multicellular preparation we were able to increase biograft vascularization and to show that the preexisting human vessels can become functional and contribute to tissue perfusion. PMID:19642856

  3. Dosimetry modeling of inhaled formaldehyde: binning nasal flux predictions for quantitative risk assessment.

    PubMed

    Kimbell, J S; Overton, J H; Subramaniam, R P; Schlosser, P M; Morgan, K T; Conolly, R B; Miller, F J

    2001-11-01

    Interspecies extrapolations of tissue dose and tumor response have been a significant source of uncertainty in formaldehyde cancer risk assessment. The ability to account for species-specific variation of dose within the nasal passages would reduce this uncertainty. Three-dimensional, anatomically realistic, computational fluid dynamics (CFD) models of nasal airflow and formaldehyde gas transport in the F344 rat, rhesus monkey, and human were used to predict local patterns of wall mass flux (pmol/[mm(2)-h-ppm]). The nasal surface of each species was partitioned by flux into smaller regions (flux bins), each characterized by surface area and an average flux value. Rat and monkey flux bins were predicted for steady-state inspiratory airflow rates corresponding to the estimated minute volume for each species. Human flux bins were predicted for steady-state inspiratory airflow at 7.4, 15, 18, 25.8, 31.8, and 37 l/min and were extrapolated to 46 and 50 l/min. Flux values higher than half the maximum flux value (flux median) were predicted for nearly 20% of human nasal surfaces at 15 l/min, whereas only 5% of rat and less than 1% of monkey nasal surfaces were associated with fluxes higher than flux medians at 0.576 l/min and 4.8 l/min, respectively. Human nasal flux patterns shifted distally and uptake percentage decreased as inspiratory flow rate increased. Flux binning captures anatomical effects on flux and is thereby a basis for describing the effects of anatomy and airflow on local tissue disposition and distributions of tissue response. Formaldehyde risk models that incorporate flux binning derived from anatomically realistic CFD models will have significantly reduced uncertainty compared with risk estimates based on default methods. PMID:11606807

  4. Nasal T cell lymphoma: a rare entity.

    PubMed

    Kazi, Maliha; Ikram, Mubasher; Junaid, Montasir

    2014-03-01

    Nasal type of Natural Killer (NK)/T cell lymphoma manifests in the nasal cavity. Approximately 95% of them are associated with EBV(Ebstein Barr Virus) with a strong predilection for the Asian population. It has certain systemic and localized symptoms which aid in diagnosis of the condition. However, the histological criteria is pivotal in confirming the diagnosis as well as aiding in confirming the association of EBV. Nasal type of NK/T cell lymphoma has a guarded prognosis. Treatment plan include radiotherapy with concurrent chemotherapy. Despite all this, the 5-year survival rate ranges from 15-75%. A 35 years old male presented with an ulcerative nasal lesion. Diagnosed as nasal type of NK/T cell lymphoma via a tissue biopsy, it was managed by chemo-radiotherapy leading to complete resolution of symptoms and disease free on his follow-up 6 months later. PMID:24718007

  5. Fluorescence Lifetimes of Normal and Carcinomatous Human Nasopharyngeal Tissues

    NASA Astrophysics Data System (ADS)

    Chen, M.; Li, H.; Li, B.; Chen, R.; Zheng, G.; Song, C.

    2016-03-01

    Time-resolved fluorescence spectra of normal and carcinomatous in vitro human nasopharyngeal tissues are compared. By fitting the time-resolved emission with exponential decays, mean lifetimes were obtained. There were marked differences between the lifetimes of the carcinomatous and the normal tissues. Thus, early diagnosis of nasopharyngeal carcinoma is possible. In general, comprehensive information from human tissue autofluorescence can be acquired via both time-resolved and steady-state fluorescence spectra.

  6. The human transcriptome across tissues and individuals

    PubMed Central

    Melé, Marta; Ferreira, Pedro G.; Reverter, Ferran; DeLuca, David S.; Monlong, Jean; Sammeth, Michael; Young, Taylor R.; Goldmann, Jakob M; Pervouchine, Dmitri D.; Sullivan, Timothy J.; Johnson, Rory; Segrè, Ayellet V.; Djebali, Sarah; Niarchou, Anastasia; Wright, Fred A.; Lappalainen, Tuuli; Calvo, Miquel; Getz, Gad; Dermitzakis, Emmanouil T.; Ardlie, Kristin G.; Guigó, Roderic

    2015-01-01

    Transcriptional regulation and posttranscriptional processing underlie many cellular and organismal phenotypes. We used RNA sequence data generated by Genotype-Tissue Expression (GTEx) project to investigate the patterns of transcriptome variation across individuals and tissues. Tissues exhibit characteristic transcriptional signatures that show stability in postmortem samples. These signatures are dominated by a relatively small number of genes—which is most clearly seen in blood—though few are exclusive to a particular tissue and vary more across tissues than individuals. Genes exhibiting high interindividual expression variation include disease candidates associated with sex, ethnicity, and age. Primary transcription is the major driver of cellular specificity, with splicing playing mostly a complementary role; except for the brain, which exhibits a more divergent splicing program. Variation in splicing, despite its stochasticity, may play in contrast a comparatively greater role in defining individual phenotypes. PMID:25954002

  7. Nasal meatus plasty: a contribution to plastic reconstruction of the nasal valve during midfacial degloving.

    PubMed

    Lorenz, Kai J; Maier, Heinz; Wilde, Frank

    2014-01-01

    Midfacial degloving is a proven method for easily accessing the midface, the nasal pyramid, the maxillary and ethmoidal sinuses, the orbits, as well as the anterior skull base. Indications for this method of access mainly include tumour resections in the area of the midface, the septum, the maxillary sinus, the paranasal to the sphenoidal sinus as well as the clivus. In addition, this method of access allows for the exposure of the bony structures of the midface in the event of extensive fractures. In general, this method of access combines an incision in the oral vestibule and circular incisions in the nasal vestibule area in order to release the nasal pyramid. After removing the facial wall of the maxillary sinus, extensive exposure of the surgical site is possible. One disadvantage of this method of access is the difficult reconstruction of the nasal valve area, which often leads to cicatricial stenoses and difficulties with breathing through the nose. Furthermore, wound healing problems and osteoradionecrosis in the area of the lateral margin of the anterior nasal aperture after replantation of the facial wall of the maxillary sinus have been described, because in this area sufficient soft tissue coverage cannot be ensured when a conventional technique is used. We describe a soft tissue flap pedicled in the cranial and caudal directions in the nasal valve area which makes both the reconstruction of the nasal vestibule and sufficient soft tissue coverage of the anterior nasal aperture possible. PMID:26504717

  8. Predicting DNA methylation level across human tissues.

    PubMed

    Ma, Baoshan; Wilker, Elissa H; Willis-Owen, Saffron A G; Byun, Hyang-Min; Wong, Kenny C C; Motta, Valeria; Baccarelli, Andrea A; Schwartz, Joel; Cookson, William O C M; Khabbaz, Kamal; Mittleman, Murray A; Moffatt, Miriam F; Liang, Liming

    2014-04-01

    Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R(2) increases from 0.38 (original R(2) between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

  9. Predicting DNA methylation level across human tissues

    PubMed Central

    Ma, Baoshan; Wilker, Elissa H.; Willis-Owen, Saffron A. G.; Byun, Hyang-Min; Wong, Kenny C. C.; Motta, Valeria; Baccarelli, Andrea A.; Schwartz, Joel; Cookson, William O. C. M.; Khabbaz, Kamal; Mittleman, Murray A.; Moffatt, Miriam F.; Liang, Liming

    2014-01-01

    Differences in methylation across tissues are critical to cell differentiation and are key to understanding the role of epigenetics in complex diseases. In this investigation, we found that locus-specific methylation differences between tissues are highly consistent across individuals. We developed a novel statistical model to predict locus-specific methylation in target tissue based on methylation in surrogate tissue. The method was evaluated in publicly available data and in two studies using the latest IlluminaBeadChips: a childhood asthma study with methylation measured in both peripheral blood leukocytes (PBL) and lymphoblastoid cell lines; and a study of postoperative atrial fibrillation with methylation in PBL, atrium and artery. We found that our method can greatly improve accuracy of cross-tissue prediction at CpG sites that are variable in the target tissue [R2 increases from 0.38 (original R2 between tissues) to 0.89 for PBL-to-artery prediction; from 0.39 to 0.95 for PBL-to-atrium; and from 0.81 to 0.98 for lymphoblastoid cell line-to-PBL based on cross-validation, and confirmed using cross-study prediction]. An extended model with multiple CpGs further improved performance. Our results suggest that large-scale epidemiology studies using easy-to-access surrogate tissues (e.g. blood) could be recalibrated to improve understanding of epigenetics in hard-to-access tissues (e.g. atrium) and might enable non-invasive disease screening using epigenetic profiles. PMID:24445802

  10. Pythiosis in the Nasal Cavity of Horses.

    PubMed

    Souto, E P F; Maia, L A; Olinda, R G; Galiza, G J N; Kommers, G D; Miranda-Neto, E G; Dantas, A F M; Riet-Correa, F

    2016-01-01

    Two cases of nasal pythiosis are reported in horses from the semi-arid region of northeastern Brazil. From January 1986 to December 2015, the Laboratory of Animal Pathology, Federal University of Campina Grande received 830 equine samples, 156 (18.79%) of which were diagnosed with pythiosis. Of these, two horses (1.28%), a male and a female adult cross-breed, had lesions in the nasal cavity. Both horses had access to water reservoirs. Clinically, they had swelling in the rhinofacial region and a serosanguineous nasal discharge. Macroscopically, in case 1, the lesion affected the nasal vestibule, extending to the alar cartilage and nasal septum. In case 2, the lesion extended through the turbinates and the meatuses of the nasal cavity, as well as the ethmoid region. In both cases, the lesions were characterized by having a yellow-grey granular surface with cavitations of different sizes containing coral-like masses of necrotic tissue (kunkers). Histologically, multifocal necrotizing eosinophilic rhinitis associated with hyphae (2-8 μm) similar to Pythium insidiosum were observed. In case 2, the lesions extended to the muscle, cartilage and bone adjacent to the nasal cavity and lungs. The diagnosis was confirmed by immunohistochemistry. It is concluded that nasal pythiosis occurs sporadically in horses in the semi-arid region of northeastern Brazil where cutaneous pythiosis is prevalent. PMID:27406311

  11. Nasal Wash Treatment

    MedlinePlus

    ... Make the nasal wash solution. Do not use tap water for the nasal wash (unless boiled or filtered ... water. You may use: Distilled water Sterilized water Tap water that has been boiled for 1 minute (at ...

  12. Post-Nasal Drip

    MedlinePlus

    ... guaifenesin (Humibid®, Robitussin®) may also thin secretions. Nasal irrigations may alleviate thickened secretions. These can be performed ... device or a Water Pik® with a nasal irrigation nozzle. Warm water with baking soda or salt ( ...

  13. Testosterone Nasal Gel

    MedlinePlus

    Testosterone nasal gel is used to treat symptoms of low testosterone in men who have hypogonadism (a condition in which the body does not produce enough natural testosterone). Testosterone nasal gel is used only for men ...

  14. Mometasone Nasal Spray

    MedlinePlus

    ... relieve symptoms of sneezing, runny, stuffy, or itchy nose caused by hay fever or other allergies. It ... nasal polyps (swelling of the lining of the nose). Mometasone nasal spray should not be used to ...

  15. Beclomethasone Nasal Spray

    MedlinePlus

    ... the lining of the nose) after nasal polyp removal surgery. Beclomethasone nasal spray should not be used ... as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this ...

  16. Nasal fracture - aftercare

    MedlinePlus

    ... page: //medlineplus.gov/ency/patientinstructions/000554.htm Nasal fracture - aftercare To use the sharing features on this ... that gives your nose its shape. A nasal fracture occurs when the bony part of your nose ...

  17. Nasal corticosteroid sprays

    MedlinePlus

    ... Allergic rhinitis symptoms , such as congestion, runny nose, sneezing, itching, or swelling of the nasal passageway Nasal ... Repeat these steps for the other nostril. Avoid sneezing or blowing your nose right after spraying.

  18. Nasal Harmony in Aguaruna.

    ERIC Educational Resources Information Center

    Moon, Gui-Sun

    A discussion of the nasal harmony of Aguaruna, a language of the Jivaroan family in South America, approaches the subject from the viewpoint of generative phonology. This theory of phonology proposes an underlying nasal consonant, later deleted, that accounts for vowel nasalization. Complex rules that suppose a complex system of vowel and…

  19. Saline nasal washes

    MedlinePlus

    Salt water washes; Nasal irrigation; Nasal lavage; Sinusitis - nasal wash ... by mixing: 3 teaspoons (tsp) canning or pickling salt (no iodine) 1 tsp baking soda 1 cup warm distilled, filtered, or boiled water To use the wash: Fill the device with ...

  20. Oxymetazoline Nasal Spray

    MedlinePlus

    ... is recommended by a doctor. Children 6 to 12 years of age should use oxymetazoline nasal spray carefully and under adult supervision. Oxymetazoline is in a class of medications called nasal decongestants. It works by narrowing the blood vessels in the nasal passages.

  1. Persistence of nasal colonization with human pathogenic bacteria and associated antimicrobial resistance in the German general population.

    PubMed

    Köck, R; Werner, P; Friedrich, A W; Fegeler, C; Becker, K

    2016-01-01

    The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878 nonhospitalized volunteers recruited from the general population in Germany. Participants provided nasal swabs at three time points (each separated by 4-6 months). Staphylococcus aureus, Enterobacteriaceae and important nonfermenters were cultured and subjected to susceptibility testing. Factors potentially influencing bacterial colonization patterns were assessed. The overall prevalence of S. aureus, Enterobacteriaceae and nonfermenters was 41.0, 33.4 and 3.7%, respectively. Thirteen participants (0.7%) were colonized with methicillin-resistant S. aureus. Enterobacteriaceae were mostly (>99%) susceptible against ciprofloxacin and carbapenems (100%). Extended-spectrum β-lactamase-producing isolates were not detected among Klebsiella oxytoca, Klebsiella pneumoniae and Escherichia coli. Several lifestyle- and health-related factors (e.g. household size, travel, livestock density of the residential area or occupational livestock contact, atopic dermatitis, antidepressant or anti-infective drugs) were associated with colonization by different microorganisms. This study unexpectedly demonstrated high nasal colonization rates with Enterobacteriaceae in the German general population, but rates of antibiotic resistance were low. Methicillin-resistant S. aureus carriage was rare but highly associated with occupational livestock contact. PMID:26862431

  2. Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa: a clinical trial of immunogenicity in lower airways of human volunteers.

    PubMed

    Bumann, Dirk; Behre, Christoph; Behre, Katharina; Herz, Steffen; Gewecke, Britta; Gessner, J Engelbert; von Specht, Bernd Ulrich; Baumann, Ulrich

    2010-01-01

    Vaccination against Pseudomonas aeruginosa is a desirable, yet challenging strategy for prevention of airway infection in patients with cystic fibrosis. We compared the formation of antibodies in lower airways induced by systemic and mucosal vaccination strategies. We immunised 48 volunteers in six vaccination groups with either a systemic, a nasal, or four newly constructed oral live vaccines based on attenuated live Salmonella (strains CVD908 and Ty21a), followed by a systemic booster vaccination. All vaccines were based on a recombinant fusion protein of the highly conserved P. aeruginosa outer membrane proteins OprF and OprI as antigen. While systemic and mucosal vaccines induced a comparable rise of serum antibody titers, a significant rise of IgA and IgG antibodies in the lower airways was noted only after nasal and oral vaccinations. We conclude that nasal and oral OprF-OprI vaccines are promising candidates for development of antipseudomonal immunisation through inducing a specific antibody response in the lung. PMID:19887136

  3. Persistence of nasal colonization with human pathogenic bacteria and associated antimicrobial resistance in the German general population

    PubMed Central

    Köck, R.; Werner, P.; Friedrich, A.W.; Fegeler, C.; Becker, K.; Bindewald, O.; Bui, T.T.; Eckhoff, C.; Epping, R.; Kähmann, L.; Meurer, M.; Steger, J.; von Auenmüller, L.

    2015-01-01

    The nares represent an important bacterial reservoir for endogenous infections. This study aimed to assess the prevalence of nasal colonization by different important pathogens, the associated antimicrobial susceptibility and risk factors. We performed a prospective cohort study among 1878 nonhospitalized volunteers recruited from the general population in Germany. Participants provided nasal swabs at three time points (each separated by 4–6 months). Staphylococcus aureus, Enterobacteriaceae and important nonfermenters were cultured and subjected to susceptibility testing. Factors potentially influencing bacterial colonization patterns were assessed. The overall prevalence of S. aureus, Enterobacteriaceae and nonfermenters was 41.0, 33.4 and 3.7%, respectively. Thirteen participants (0.7%) were colonized with methicillin-resistant S. aureus. Enterobacteriaceae were mostly (>99%) susceptible against ciprofloxacin and carbapenems (100%). Extended-spectrum β-lactamase–producing isolates were not detected among Klebsiella oxytoca, Klebsiella pneumoniae and Escherichia coli. Several lifestyle- and health-related factors (e.g. household size, travel, livestock density of the residential area or occupational livestock contact, atopic dermatitis, antidepressant or anti-infective drugs) were associated with colonization by different microorganisms. This study unexpectedly demonstrated high nasal colonization rates with Enterobacteriaceae in the German general population, but rates of antibiotic resistance were low. Methicillin-resistant S. aureus carriage was rare but highly associated with occupational livestock contact. PMID:26862431

  4. Depth-resolved fluorescence of human ectocervical tissue

    NASA Astrophysics Data System (ADS)

    Wu, Yicong; Xi, Peng; Cheung, Tak-Hong; Yim, So Fan; Yu, Mei-Yung; Qu, Jianan Y.

    2005-04-01

    The depth-resolved autofluorescence of normal and dysplastic human ectocervical tissue within 120um depth were investigated utilizing a portable confocal fluorescence spectroscopy with the excitations at 355nm and 457nm. From the topmost keratinizing layer of all ectocervical tissue samples, strong keratin fluorescence with the spectral characteristics similar to collagen was observed, which created serious interference in seeking the correlation between tissue fluorescence and tissue pathology. While from the underlying non-keratinizing epithelial layer, the measured NADH fluorescence induced by 355nm excitation and FAD fluorescence induced by 457nm excitation were strongly correlated to the tissue pathology. The ratios between NADH over FAD fluorescence increased statistically in the CIN epithelial relative to the normal and HPV epithelia, which indicated increased metabolic activity in precancerous tissue. This study demonstrates that the depth-resolved fluorescence spectroscopy can reveal fine structural information on epithelial tissue and potentially provide more accurate diagnostic information for determining tissue pathology.

  5. Analysis of human breast tissues with Raman microspectroscopy

    NASA Astrophysics Data System (ADS)

    Liu, Gang; Zhang, Lin; Liu, Jianhong; Yu, Fan; Sun, Shizhong

    2006-01-01

    Raman microspectroscopy was used to study normal, benign and malignant human breast tissues. The Raman spectrum of normal breast tissue recorded with 514.5 nm line of Ar + laser excitation contains features attributed to carotenoids and lipids. The CH II bending mode near 1447 cm -1 in normal tissue shifts up to 1454 cm -1 in diseased tissues (benign and malignant). The band near 1660 cm -1 in normal tissue is narrow and sharp; whereas the band is broaden in the diseased tissues. In the region of C-H stretching mode, the 2902-/2860-cm -1 intensity ratio shows differences among normal, benign and malignant breast tissues. The ratio is the smallest in carcinoma tissue. The observed spectra differences may be used to probe breast lesion. The results show that Raman spectroscopic technique may have clinical applications.

  6. Identification of progesterone receptor in human subcutaneous adipose tissue.

    PubMed

    O'Brien, S N; Welter, B H; Mantzke, K A; Price, T M

    1998-02-01

    Sex steroids are postulated to play a role in adipose tissue regulation and distribution, because the amount and location of adipose tissue changes during puberty and menopause. Because of the nature of adipose tissue, receptors for the female sex steroids have been difficult to demonstrate. To date, estrogen receptor messenger RNA and protein have been identified in human subcutaneous adipose tissue, but the presence of progesterone receptor (PR) has not been reported. In this study, we demonstrate PR message by Northern blot analysis in RNA isolated from the abdominal subcutaneous adipose tissue of premenopausal women. These preliminary studies revealed that PR messenger RNA levels are higher in the stromal-vascular fraction as opposed to the adipocyte fraction. Western blot analysis demonstrates both PR protein isoforms (human PR-A and human PR-B) in human subcutaneous adipose tissue. Using an enzyme-linked immunosorbent assay, total PR could be quantitated. These studies substantiate that sex steroid receptors are present in human adipose tissue, thereby providing a direct route for regulation of adipose tissue by female sex steroids. PMID:9467566

  7. Distribution of miRNA expression across human tissues

    PubMed Central

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-01-01

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas). PMID:26921406

  8. Distribution of miRNA expression across human tissues.

    PubMed

    Ludwig, Nicole; Leidinger, Petra; Becker, Kurt; Backes, Christina; Fehlmann, Tobias; Pallasch, Christian; Rheinheimer, Steffi; Meder, Benjamin; Stähler, Cord; Meese, Eckart; Keller, Andreas

    2016-05-01

    We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10(-8)) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas). PMID:26921406

  9. Three-Dimensionally Engineered Normal Human Lung Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J.; McCarthy, M.; Lin, Y-H.; Deatly, A. M.

    2008-01-01

    In vitro three-dimensional (3D) human lung epithelio-mesenchymal tissue-like assemblies (3D hLEM TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and the detection of membrane bound glycoproteins over time confirm productive infection with the virus. Therefore, we assert TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host s immune system.

  10. Three-Dimensionally Engineered Normal Human Broncho-epithelial Tissue-Like Assemblies: Target Tissues for Human Respiratory Viral Infections

    NASA Technical Reports Server (NTRS)

    Goodwin, T. J.; McCarthy, M.; Lin, Y-H

    2006-01-01

    In vitro three-dimensional (3D) human broncho-epithelial (HBE) tissue-like assemblies (3D HBE TLAs) from this point forward referred to as TLAs were engineered in Rotating Wall Vessel (RWV) technology to mimic the characteristics of in vivo tissues thus providing a tool to study human respiratory viruses and host cell interactions. The TLAs were bioengineered onto collagen-coated cyclodextran microcarriers using primary human mesenchymal bronchial-tracheal cells (HBTC) as the foundation matrix and an adult human bronchial epithelial immortalized cell line (BEAS-2B) as the overlying component. The resulting TLAs share significant characteristics with in vivo human respiratory epithelium including polarization, tight junctions, desmosomes, and microvilli. The presence of tissue-like differentiation markers including villin, keratins, and specific lung epithelium markers, as well as the production of tissue mucin, further confirm these TLAs differentiated into tissues functionally similar to in vivo tissues. Increasing virus titers for human respiratory syncytial virus (wtRSVA2) and parainfluenza virus type 3 (wtPIV3 JS) and the detection of membrane bound glycoproteins over time confirm productive infections with both viruses. Therefore, TLAs mimic aspects of the human respiratory epithelium and provide a unique capability to study the interactions of respiratory viruses and their primary target tissue independent of the host's immune system.

  11. The nasal cavity microbiota of healthy adults

    PubMed Central

    2014-01-01

    Background The microbiota of the nares has been widely studied. However, relatively few studies have investigated the microbiota of the nasal cavity posterior to the nares. This distinct environment has the potential to contain a distinct microbiota and play an important role in health. Results We obtained 35,142 high-quality bacterial 16S rRNA-encoding gene sequence reads from the nasal cavity and oral cavity (the dorsum of the tongue and the buccal mucosa) of 12 healthy adult humans and deposited these data in the Sequence Read Archive (SRA) of the National Center for Biotechnology Information (NCBI) (Bioproject: PRJNA248297). In our initial analysis, we compared the bacterial communities of the nasal cavity and the oral cavity from ten of these subjects. The nasal cavity bacterial communities were dominated by Actinobacteria, Firmicutes, and Proteobacteria and were statistically distinct from those on the tongue and buccal mucosa. For example, the same Staphylococcaceae operational taxonomic unit (OTU) was present in all of the nasal cavity samples, comprising up to 55% of the community, but Staphylococcaceae was comparatively uncommon in the oral cavity. Conclusions There are clear differences between nasal cavity microbiota and oral cavity microbiota in healthy adults. This study expands our knowledge of the nasal cavity microbiota and the relationship between the microbiota of the nasal and oral cavities. PMID:25143824

  12. National Human Adipose Tissue Survey (Nhats)

    EPA Science Inventory

    Background:

    The U.S. Environmental Protection Agency (EPA)'s National Human Monitoring Program (NHMP), established by the U.S. Public Health Service in 1967, used an exposure-based approach to assess human exposure to toxic substances. Its primary component was the Natio...

  13. Nasal Tip Deficiency.

    PubMed

    Cerkes, Nazim

    2016-01-01

    Nasal tip deficiency can be congenital or secondary to previous nasal surgeries. Underdeveloped medial crura usually present with underprojected tip and lack of tip definition. Weakness or malposition of lateral crura causes alar rim retraction and lateral nasal wall weakness. Structural grafting of alar cartilages strengthens the tip framework, reinforces the disrupted support mechanisms, and controls the position of the nasal tip. In secondary cases, anatomic reconstruction of the weakened or interrupted alar cartilages and reconstitution of a stable nasal tip tripod must be the goal for a predictable outcome. PMID:26616702

  14. Comparative pathology of the nasal mucosa in laboratory animals exposed to inhaled irritants

    SciTech Connect

    Harkema, J.R. )

    1990-04-01

    The nasal cavity is susceptible to chemically induced injury as a result of exposure to inhaled irritants. Some responses of the nasal mucosa to inhaled toxicants are species specific. These species-related differences in response may be due to variations in structural, physiologic, and biochemical factors, such as gross nasal cavity structure, distribution of luminal epithelial cell populations along the nasal airway, intranasal airflow patterns, nasal mucociliary apparatus, and nasal xenobiotic metabolism among animal species. This paper reviews the comparative anatomy and irritant-induced pathology of the nasal cavity in laboratory animals. The toxicologist, pathologist, and environmental risk assessor must have a good working knowledge of the similarities and differences in normal nasal structure and response to injury among species before they can select animal models for nasal toxicity studies, recognize toxicant-induced lesions in the nasal airway, and extrapolate experimental results to estimate the possible effects of an inhaled toxicant on the human nasal airway.

  15. Bovine Leukemia Virus DNA in Human Breast Tissue

    PubMed Central

    Shen, Hua Min; Jensen, Hanne M.; Choi, K. Yeon; Sun, Dejun; Nuovo, Gerard

    2014-01-01

    Bovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease. PMID:24750974

  16. Detection of Helicobacter pylori in Nasal Polyps.

    PubMed

    Bansal, Divya; Sharma, Sonal; Agarwal, Sarla; Saha, Rumpa; Gupta, Neelima

    2016-09-01

    To detect the presence of Helicobacter pylori in nasal polyps. A case-control study was conducted enrolling 35 patients with nasal polyps (cases) and patients undergoing septoplasty (controls). Fresh tissue samples were used for urea broth test and imprint cytology, while formalin fixed tissue sections were used for morphology, special stains and immunohistochemistry for H. pylori. Fresh stool samples from both groups were tested to correlate the gastrointestinal status. H. pylori was detected in 40.0 % (14/35) of cases and 8.5 % of controls (3/35) (p = 0.004) by immunohistochemistry. Amongst cases, eight were positive with urea broth test, six with imprint cytology (Giemsa stain), three with H & E, and nine with modified McMullen's stain. Hyperplasia of the lining epithelium and lymphoid aggregates were significantly noticed in nasal polyps positive for H. pylori. Stool antigen test was positive in subjects who were positive for H. pylori in the nasal mucosa. There appears to be an association between H. pylori and nasal polyps. Immunohistochemistry is more sensitive and specific method to detect H. pylori. H. pylori induced inflammatory tissue reaction pattern indicates a possible causal association. Further studies are needed to prove the causal relationship between H. pylori and nasal polyps. PMID:26830396

  17. Altered autophagy in human adipose tissues in obesity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  18. Tissue-based imaging model of human trabecular meshwork.

    PubMed

    Chu, Edward R; Gonzalez, Jose M; Tan, James C H

    2014-01-01

    We have developed a tissue-based model of the human trabecular meshwork (TM) using viable postmortem corneoscleral donor tissue. Two-photon microscopy is used to optically section and image deep in the tissue to analyze cells and extracellular matrix (ECM) within the original three-dimensional (3D) environment of the TM. Multimodal techniques, including autofluorescence (AF), second harmonic generation (SHG), intravital dye fluorescence, and epifluorescence, are combined to provide unique views of the tissue at the cellular and subcellular level. SHG and AF imaging are non-invasive tissue imaging techniques with potential for clinical application, which can be modeled in the system. We describe the following in the tissue-based model: analysis of live cellularity to determine tissue viability; characteristics of live cells based on intravital labeling; features and composition of the TM's structural ECM; localization of specific ECM proteins to regions such as basement membrane; in situ induction and expression of tissue markers characteristic of cultured TM cells relevant to glaucoma; analysis of TM actin and pharmacological effects; in situ visualization of TM, inner wall endothelium, and Schlemm's canal; and application of 3D reconstruction, modeling, and quantitative analysis to the TM. The human model represents a cost-effective use of valuable and scarce yet available human tissue that allows unique cell biology, pharmacology, and translational studies of the TM. PMID:24517246

  19. Micro-CT scouting for transmission electron microscopy of human tissue specimens.

    PubMed

    Morales, A G; Stempinski, E S; Xiao, X; Patel, A; Panna, A; Olivier, K N; McShane, P J; Robinson, C; George, A J; Donahue, D R; Chen, P; Wen, H

    2016-07-01

    Transmission electron microscopy (TEM) provides sub-nanometre-scale details in volumetric samples. Samples such as pathology tissue specimens are often stained with a metal element to enhance contrast, which makes them opaque to optical microscopes. As a result, it can be a lengthy procedure to find the region of interest inside a sample through sectioning. We describe micro-CT scouting for TEM that allows noninvasive identification of regions of interest within a block sample to guide the sectioning step. In a tissue pathology study, a bench-top micro-CT scanner with 10 μm resolution was used to determine the location of patches of the mucous membrane in osmium-stained human nasal scraping samples. Once the regions of interest were located, the sample block was sectioned to expose that location, followed by ultra-thin sectioning and TEM to inspect the internal structure of the cilia of the membrane epithelial cells with nanometre resolution. This method substantially reduced the time and labour of the search process from typically 20 sections for light microscopy to three sections with no added sample preparation. PMID:26854176

  20. Characterization of Human Papillomavirus Type 154 and Tissue Tropism of Gammapapillomaviruses

    PubMed Central

    Ure, Agustín Enrique; Forslund, Ola

    2014-01-01

    The novel human papillomavirus type 154 (HPV154) was characterized from a wart on the crena ani of a three-year-old boy. It was previously designated as the putative HPV type FADI3 by sequencing of a subgenomic FAP amplicon. We obtained the complete genome by combined methods including rolling circle amplification (RCA), genome walking through an adapted method for detection of integrated papillomavirus sequences by ligation-mediated PCR (DIPS-PCR), long-range PCR, and finally by cloning of four overlapping amplicons. Phylogenetically, the HPV154 genome clustered together with members of the proposed species Gammapapillomavirus 11, and demonstrated the highest identity in L1 to HPV136 (68.6%). The HPV154 was detected in 3% (2/62) of forehead skin swabs from healthy children. In addition, the different detection sites of 62 gammapapillomaviruses were summarized in order to analyze their tissue tropism. Several of these HPV types have been detected from multiple sources such as skin, oral, nasal, and genital sites, suggesting that the gammapapillomaviruses are generalists with a broader tissue tropism than previously appreciated. The study expands current knowledge concerning genetic diversity and tropism among HPV types in the rapidly growing gammapapillomavirus genus. PMID:24551244

  1. Microwave non-contact imaging of subcutaneous human body tissues.

    PubMed

    Kletsov, Andrey; Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-10-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated. PMID:26609415

  2. Microwave non-contact imaging of subcutaneous human body tissues

    PubMed Central

    Chernokalov, Alexander; Khripkov, Alexander; Cho, Jaegeol; Druchinin, Sergey

    2015-01-01

    A small-size microwave sensor is developed for non-contact imaging of a human body structure in 2D, enabling fitness and health monitoring using mobile devices. A method for human body tissue structure imaging is developed and experimentally validated. Subcutaneous fat tissue reconstruction depth of up to 70 mm and maximum fat thickness measurement error below 2 mm are demonstrated by measurements with a human body phantom and human subjects. Electrically small antennas are developed for integration of the microwave sensor into a mobile device. Usability of the developed microwave sensor for fitness applications, healthcare, and body weight management is demonstrated. PMID:26609415

  3. Deposition of {open_quotes}unattached{close_quotes} radon daughters in models of human nasal and oral airways

    SciTech Connect

    Strong, J.C.; Swift, D.L.

    1992-12-31

    In order to estimate accurately an effective dose equivalent for exposures to radon daughters, knowledge of their deposition in the lung is required. However, the nose and mouth are effective filters for removing aerosol particles, especially in the range of sizes of {open_quotes}unattached{close_quotes} radon daughters. Therefore, it is equally important to have reliable data on deposition in this region of the respiratory tract. We will describe our work in studying nasal and oral deposition of {open_quotes}unattached{close_quotes} radon daughters in casts of these airways. Several hollow casts of adult and child nasal and oral airways were fabricated at The John Hopkins University from layers of Perspect{trademark} (an acrylic plastic). The shapes of the airway passages were obtained from nuclear magnetic resonance sectional images of healthy subjects. The casts were exposed to radon gas and daughters produced by flushing filtered air through a commercially available {sup 226}Ra source. The gas stream was drawn through a 1.4-L cylindrical tube to allow measurable growth of {sup 218}Po activity before it was passed through casts of both nasal passages or the oral cavity. The deposition of {open_quotes}unattached{close_quotes} {sup 218}Po was measured by comparing the activity collected on filters mounted in series and in parallel with a cast. Measurements were made at various flow rates (Q; 4 to 20 L min{sup -1}). The diffusion coefficient (D) of {sup 218}Po was measured each time the flow rate was changed, by replacing the cast with a stainless steel gauze screen and measuring the activity penetrating the screen. The measured diffusion coefficient ranged from 0.02 to 0.05 cm{sup 2} s{sup -1} and was found to vary with the residence time of {sup 218}Po in the growth tube. The deposition efficiency ({eta}) of {sup 218}Po measured in these casts ranged from 50 to 70%, and was similar to values we found previously, using casts of nasal and oral airways from cadavers.

  4. Total DDT and dieldrin content of human adipose tissue

    SciTech Connect

    Ahmad, N.; Harsas, W.; Marolt, R.S.; Morton, M.; Pollack, J.K.

    1988-12-01

    As far as the authors could ascertain only 4 well-documented analytical studies have been carried out in Australia determining the total DDT and dieldrin content of human adipose tissue. The latest of these studies was published over 16 years ago. Therefore it is timely and important to re-examine the total DDT and dieldrin concentration within the adipose tissue of the Australian population. The present investigation has analyzed 290 samples of human adipose tissue obtained from Westmead Hospital situated in an outer suburb of Sydney, New South Wales for their content of total DDT and dieldrin.

  5. Nasal Septal Deviation and Facial Skeletal Asymmetries.

    PubMed

    Hartman, Christopher; Holton, Nathan; Miller, Steven; Yokley, Todd; Marshall, Steven; Srinivasan, Sreedevi; Southard, Thomas

    2016-03-01

    During ontogeny, the nasal septum exerts a morphogenetic influence on the surrounding facial skeleton. While the influence of the septum is well established in long snouted animal models, its role in human facial growth is less clear. If the septum is a facial growth center in humans, we would predict that deviated septal growth would be associated with facial skeletal asymmetries. Using computed tomographic (CT) scans of n = 55 adult subjects, the purpose of this study was to test whether there is a correlation between septal deviation and facial asymmetries using three-dimensional (3D) geometric morphometric techniques. We calculated deviation as a percentage of septal volume relative to the volume of a modeled non-deviated septum. We then recorded skeletal landmarks representing the nasal, palatal, and lateral facial regions. Landmark data were superimposed using Procrustes analysis. First, we examined the correlation between nasal septal deviation and the overall magnitude of asymmetry. Next, we assessed whether there was a relationship between nasal septal deviation and more localized aspects of asymmetry using multivariate regression analysis. Our results indicate that while there was no correlation between septal deviation and the overall magnitude of asymmetry, septal deviation was associated with asymmetry primarily in the nasal floor and the palatal region. Septal deviation was unassociated with asymmetries in the lateral facial skeleton. Though we did not test the causal relationship between nasal septal deviation and facial asymmetry, our results suggest that the nasal septum may have an influence on patterns of adult facial form. PMID:26677010

  6. Low prevalence of oral and nasal human papillomavirus in employees performing CO2-laser evaporation of genital warts or loop electrode excision procedure of cervical dysplasia.

    PubMed

    Kofoed, Kristian; Norrbom, Christina; Forslund, Ola; Møller, Charlotte; Frøding, Ligita P; Pedersen, Anders Elm; Markauskas, Algirdas; Blomberg, Maria; Baumgartner-Nielsen, Jane; Madsen, Jakob Torp; Strauss, Gitte; Madsen, Klaus G; Sand, Carsten

    2015-02-01

    Risk of human papillomavirus (HPV) transmission during laser vaporisation of genital warts or loop electrode excision procedure is controversial. An oral rinse, a nasal swabs, history of HPV related diseases and data on HPV exposure were collected from 287 employees at departments of dermato-venerology and gynaecology in Denmark. A mucosal HPV type was found among 5.8% of employees with experience of laser treatment of genital warts as compared to 1.7% of those with no experience (p = 0.12). HPV prevalence was not higher in employees participating in electrosurgical treatment or cryotherapy of genital warts, or loop electrode excision procedure compared with those who did not. HPV 6 or 11 were not detected in any samples. Hand warts after the age of 24 years was more common among dermatology than among non-dermatology personnel (18% vs. 8.0%, p = 0.03). Mucosal HPV types are infrequent in the oral and nasal cavity of health care personnel, however, employees at departments of dermato-venereology are at risk of acquiring hand warts. PMID:24941064

  7. Efficient In Vitro Electropermeabilization of Reconstructed Human Dermal Tissue.

    PubMed

    Madi, Moinecha; Rols, Marie-Pierre; Gibot, Laure

    2015-10-01

    DNA electrotransfer is a successful technic for gene delivery. However, its use in clinical applications is limited since little is known about the mechanisms governing DNA electrotransfer in the complex environment occurring in a tissue. The objectives of this work were to investigate the role of the extracellular matrix (ECM) in that process. Tumor ECM composition was shown to modulate in vivo gene electrotransfer efficiency. In order to assess the effects of ECM composition and organization, as well as intercellular junctions and communication, in normal tissue response to electric pulses, we developed an innovative three-dimensional (3D) reconstructed human connective tissue model. 3D human dermal tissue was reconstructed in vitro by a tissue engineering approach and was representative of in vivo cell organization since cell-cell contacts were present as well as complex ECM. This human cell model presented multiple layers of primary dermal fibroblasts embedded in a native, collagen-rich ECM. This dermal tissue could become a useful tool to study skin DNA electrotransfer mechanisms. As proof of the concept, we show here that the cells within this standardized 3D tissue can be efficiently electropermeabilized by milliseconds electric pulses. We believe that a better comprehension of gene electrotransfer in such a model tissue would help improve electrogene therapy approaches such as the systemic delivery of therapeutic proteins and DNA vaccination. PMID:25788148

  8. Primary Nasal Reconstruction in Self-Inflicted Nasal Injury.

    PubMed

    Kapadia, Abizer; John, Jerry R; Gaba, Sunil; Sharma, Ramesh Kumar

    2015-10-01

    Self-inflicted injury of the nose is extremely rare. It may be associated with severe psychopathology and suicidal ideation. The authors report a case of a 24-year-old man, who presented with soft-tissue loss over both the alae of his nose. He had cut off the alar rims with an ordinary razor blade. He was overtly concerned about his nose being excessively broad and fat. A diagnosis of body dysmorphic disorder with nonsuicidal self-injury was made. Patient was observed during 72 hours in hospital with psychiatric support and local dressings. The authors undertook primary nasal reconstruction with nasolabial flaps on both sides for coverage. In conclusion, self-inflicted nasal injury mandates a judicious balancing of psychiatric support and surgical reconstruction. This can prevent untoward sequelae including further self-harm and suicide. PMID:26468831

  9. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  10. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  11. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  12. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  13. 21 CFR 876.5885 - Tissue culture media for human ex vivo tissue and cell culture processing applications.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... cell culture processing applications. 876.5885 Section 876.5885 Food and Drugs FOOD AND DRUG... DEVICES Therapeutic Devices § 876.5885 Tissue culture media for human ex vivo tissue and cell culture processing applications. (a) Identification. Tissue culture media for human ex vivo tissue and cell...

  14. Nasal Chondromesenchymal Hamartoma in a Child

    SciTech Connect

    Finitsis, Stefanos; Giavroglou, Constantinos; Potsi, Stamatia; Constantinidis, Ioannis; Mpaltatzidis, Angelos; Rachovitsas, Dimitrios; Tzioufa, Valentini

    2009-05-15

    Nasal chondromesenchymal hamartoma (NCMH) is a benign tumor that was described in 1998. The occurrence of this lesion in the nasal cavity of infants and children is especially rare, with only 21 cases reported in the international literature. We report a 12-month-old boy with respiratory distress due to nasal obstruction. Computed tomographic scan and magnetic resonance imaging examination demonstrated a soft-tissue mass obstructing the left nasal cavity. Digital subtraction angiography and preoperative superselective embolization with microparticles were also performed. The tumor was completely resected surgically. Histopathology and immunohistochemical analyses of the tumor disclosed a NCMH. The imaging characteristics of the tumor are described and the radiology literature is reviewed.

  15. Nasal vs oral intubation.

    PubMed

    Holzapfel, L

    2003-05-01

    Both nasal and oral route for intubation have advantages and disadvantages. Oral intubation is easier to perform, faster and less painful than nasal intubation under direct laryngoscopy, while blind nasal intubation represents a good alternative in conscious patient, without sedation. In trauma patient, oral route should be preferred, with cervical immobilisation. By the contrary, nasal intubation can cause bleeding, retro-pharyngeal and turbinate bones injury, but it seems preferable in preventing laryngeal complications. Moreover nasal intubation seem to increase risk for sinusitis while, there is no clear advantage for any of the two routes, concerning nosocomial pneumonia, bacteriemia and otitis. Nevertheless nasal route increases comfort for the patient and decreases injury and necrosis of tongue and lips; tube fastening is simpler thus reducing accidental extubation. PMID:12768165

  16. 78 FR 44134 - Submission for OMB Review; 30-day Comment Request: Financial Sustainability of Human Tissue...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-23

    ...: Financial Sustainability of Human Tissue Biobanking (NCI) SUMMARY: Under the provisions of Section 3507(a)(1... Collection: Financial Sustainability of Human Tissue Biobanking, 0925-NEW, National Cancer Institute...

  17. Predicting tissue-specific enhancers in the human genome

    PubMed Central

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2007-01-01

    Determining how transcriptional regulatory signals are encoded in vertebrate genomes is essential for understanding the origins of multicellular complexity; yet the genetic code of vertebrate gene regulation remains poorly understood. In an attempt to elucidate this code, we synergistically combined genome-wide gene-expression profiling, vertebrate genome comparisons, and transcription factor binding-site analysis to define sequence signatures characteristic of candidate tissue-specific enhancers in the human genome. We applied this strategy to microarray-based gene expression profiles from 79 human tissues and identified 7187 candidate enhancers that defined their flanking gene expression, the majority of which were located outside of known promoters. We cross-validated this method for its ability to de novo predict tissue-specific gene expression and confirmed its reliability in 57 of the 79 available human tissues, with an average precision in enhancer recognition ranging from 32% to 63% and a sensitivity of 47%. We used the sequence signatures identified by this approach to successfully assign tissue-specific predictions to ∼328,000 human–mouse conserved noncoding elements in the human genome. By overlapping these genome-wide predictions with a data set of enhancers validated in vivo, in transgenic mice, we were able to confirm our results with a 28% sensitivity and 50% precision. These results indicate the power of combining complementary genomic data sets as an initial computational foray into a global view of tissue-specific gene regulation in vertebrates. PMID:17210927

  18. Carcinoma of the nasal vestibule

    SciTech Connect

    Mendenhall, N.P.; Parsons, J.T.; Cassisi, N.J.; Million, R.R.

    1984-05-01

    Squamous cell carcinomas of the nasal vestibule are essentially skin cancers that require special therapeutic considerations because of the regional anatomy. They have sometimes been considered poorly suited for treatment by irradiation because of potential or actual cartilage and/or bone invasion and therefore have been treated by surgical resection, sometimes producing defects that are difficult to reconstruct satisfactorily. From 1966 to April 1980, 13 patients with squamous cell carcinoma of the nasal vestibule were treated with radiotherapy at the University of Florida. Eight lesions were de novo; 5 were recurrent after 1 or more surgical procedures. Treatment consisted of radium needle implantation and/or external beam therapy. Neck management was individualized. All de novo and 4 of 5 recurrent lesions were controlled locally. Cosmetic resultes were good in patients with de novo lesions. There were no instances of significant cartilage or soft tissue necrosis despite cartilage involvement by tumor in 6 cases.

  19. Predicting Tissue-Specific Enhancers in the Human Genome

    SciTech Connect

    Pennacchio, Len A.; Loots, Gabriela G.; Nobrega, Marcelo A.; Ovcharenko, Ivan

    2006-07-01

    Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

  20. Expression of tmp21 in normal adult human tissues

    PubMed Central

    Xie, Jian; Yang, Yuan; Li, Jianbo; Hou, Jing; Xia, Kun; Song, Weihong; Liu, Shengchun

    2014-01-01

    TMP21, known as p23 protein, is one important member of the p24 protein families. The degradation of TMP21 is mediated by the ubiquitin-proteasome pathway, as with the other presenilin-associated γ-secretase complex members. NFAT plays a very important role in regulation of human TMP21 gene expression. Compared with the function of TMP21, the studies about the distribution of this protein in human tissues are limited. We collected 19 normal adult human tissues from a healthy adult man died in a traffic accident and did examination of all the tissues collected for ICH, western blot and RT-PCR. It was shown that the expression of TMP21 is at high levels in heart, liver, lung, kidney and adrenal gland; moderate levels in brain, pancreas, prostate gland, testicle, small intestine, colon, stomach, gall bladder, thyroid gland and trachea; low levels in skeletal muscle, skin and lymphonodus. TMP21 is widely existed in normal adult human tissues. The current study provided for the first time a comprehensive expression of TMP21 in normal adult human tissues. It will benefit on helping in the design and interpretation of future studies focused on expounding the function of TMP21. PMID:25356171

  1. Functional and pharmacological characterization of volume-regulated anion channels in human normal and cystic fibrosis bronchial and nasal epithelial cells.

    PubMed

    Stott, Jennifer B; deCourcey, Francine; Ennis, Madeleine; Zholos, Alexander V

    2014-10-01

    Volume-regulated anion channels (VRACs) are widely present in various cell types and have important functions ranging from regulatory volume decrease to control of cell proliferation and apoptosis. Here we aimed to compare the biophysical features and pharmacological profiles of VRAC currents in healthy and cystic fibrosis (CF) respiratory epithelial cells in order to characterize these currents both functionally and pharmacologically. Whole-cell electrophysiology was used to characterize the VRAC current in normal (16HBE14o-; HBE) and CF cell lines (CFBE14o-; CFBE), as well as in native human nasal epithelial cells. Application of hypotonic solution produced current responses of similar sizes in both HBE and CFBE cells. Biophysical properties of VRACs, such as instantaneous activation and deactivation upon voltage step, some inactivation at potentials positive to 40 mV and outwardly-rectifying I-V curves, were indistinguishable in both cell types. Extensive pharmacological analysis of the currents revealed a similar pharmacological profile in response to three blockers--NPPB, DCPIB and DIDS. Native primary human nasal epithelial cells from both healthy and CF volunteers also showed typical VRAC responses of comparable sizes. VRACs in these cells were more sensitive to external solution hypotonicity compared to HBE and CFBE cells. In all cell types studied robust VRAC currents could be induced at constant cell volume by G-protein activation with GTPγS infusion. This study provides the first extensive comparative functional and pharmacological analysis of VRAC currents in normal and CF airway epithelial cells and shows that VRACs are unimpaired molecularly or functionally in CF. PMID:25034811

  2. Engineered human broncho-epithelial tissue-like assemblies

    NASA Technical Reports Server (NTRS)

    Goodwin, Thomas J. (Inventor)

    2012-01-01

    Three-dimensional human broncho-epithelial tissue-like assemblies (TLAs) are produced in a rotating wall vessel (RWV) with microcarriers by coculturing mesenchymal bronchial-tracheal cells (BTC) and bronchial epithelium cells (BEC). These TLAs display structural characteristics and express markers of in vivo respiratory epithelia. TLAs are useful for screening compounds active in lung tissues such as antiviral compounds, cystic fibrosis treatments, allergens, and cytotoxic compounds.

  3. Infrared absorption spectra of human malignant tumor tissues

    NASA Astrophysics Data System (ADS)

    Skornyakov, I. V.; Tolstorozhev, G. B.; Butra, V. A.

    2008-05-01

    We used infrared spectroscopy methods to study the molecular structure of tissues from human organs removed during surgery. The IR spectra of the surgical material from breast, thyroid, and lung are compared with data from histological examination. We show that in malignant neoplasms, a change occurs in the hydrogen bonds of protein macromolecules found in the tissue of the studied organs. We identify the spectral signs of malignant pathology.

  4. Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis

    PubMed Central

    Garcia, Briana; Francois-Vaughan, Heather; Onikoyi, Omobola; Kostadinov, Stefan; De Paepe, Monique E.; Gruppuso, Philip A.; Sanders, Jennifer A.

    2014-01-01

    Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology. PMID:25193996

  5. Xenotransplantation of human fetal adipose tissue: a model of in vivo adipose tissue expansion and adipogenesis.

    PubMed

    Garcia, Briana; Francois-Vaughan, Heather; Onikoyi, Omobola; Kostadinov, Stefan; De Paepe, Monique E; Gruppuso, Philip A; Sanders, Jennifer A

    2014-12-01

    Obesity during childhood and beyond may have its origins during fetal or early postnatal life. At present, there are no suitable in vivo experimental models to study factors that modulate or perturb human fetal white adipose tissue (WAT) expansion, remodeling, development, adipogenesis, angiogenesis, or epigenetics. We have developed such a model. It involves the xenotransplantation of midgestation human WAT into the renal subcapsular space of immunocompromised SCID-beige mice. After an initial latency period of approximately 2 weeks, the tissue begins expanding. The xenografts are healthy and show robust expansion and angiogenesis for at least 2 months following transplantation. Data and cell size and gene expression are consistent with active angiogenesis. The xenografts maintain the expression of genes associated with differentiated adipocyte function. In contrast to the fetal tissue, adult human WAT does not engraft. The long-term viability and phenotypic maintenance of fetal adipose tissue following xenotransplantation may be a function of its autonomous high rates of adipogenesis and angiogenesis. Through the manipulation of the host mice, this model system offers the opportunity to study the mechanisms by which nutrients and other environmental factors affect human adipose tissue development and biology. PMID:25193996

  6. Laser ablation of human atherosclerotic plaque without adjacent tissue injury

    NASA Technical Reports Server (NTRS)

    Grundfest, W. S.; Litvack, F.; Forrester, J. S.; Goldenberg, T.; Swan, H. J. C.

    1985-01-01

    Seventy samples of human cadaver atherosclerotic aorta were irradiated in vitro using a 308 nm xenon chloride excimer laser. Energy per pulse, pulse duration and frequency were varied. For comparison, 60 segments were also irradiated with an argon ion and an Nd:YAG laser operated in the continuous mode. Tissue was fixed in formalin, sectioned and examined microscopically. The Nd:YAG and argon ion-irradiated tissue exhibited a central crater with irregular edges and concentric zones of thermal and blast injury. In contrast, the excimer laser-irradiated tissue had narrow deep incisions with minimal or no thermal injury. These preliminary experiments indicate that the excimer laser vaporizes tissue in a manner different from that of the continuous wave Nd:YAG or argon ion laser. The sharp incision margins and minimal damage to adjacent normal tissue suggest that the excimer laser is more desirable for general surgical and intravascular uses than are the conventionally used medical lasers.

  7. Integrative analysis of haplotype-resolved epigenomes across human tissues

    PubMed Central

    Schmitt, Anthony; Selvaraj, Siddarth; Lee, Ah Young; Yen, Chia-An; Lin, Shin; Lin, Yiing; Qiu, Yunjiang; Xie, Wei; Yue, Feng; Hariharan, Manoj; Ray, Pradipta; Kuan, Samantha; Edsall, Lee; Yang, Hongbo; Chi, Neil C.; Zhang, Michael Q.; Ecker, Joseph R.; Ren, Bing

    2015-01-01

    Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here, for the first time, we delineate allelic chromatin modifications and transcriptomes amongst a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy1. The resulting masses of haplotype-resolved epigenomic maps reveal extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich datasets described here will enhance our understanding of the mechanisms of how cis-regulatory elements control gene expression programs. PMID:25693566

  8. Integrative analysis of haplotype-resolved epigenomes across human tissues.

    PubMed

    Leung, Danny; Jung, Inkyung; Rajagopal, Nisha; Schmitt, Anthony; Selvaraj, Siddarth; Lee, Ah Young; Yen, Chia-An; Lin, Shin; Lin, Yiing; Qiu, Yunjiang; Xie, Wei; Yue, Feng; Hariharan, Manoj; Ray, Pradipta; Kuan, Samantha; Edsall, Lee; Yang, Hongbo; Chi, Neil C; Zhang, Michael Q; Ecker, Joseph R; Ren, Bing

    2015-02-19

    Allelic differences between the two homologous chromosomes can affect the propensity of inheritance in humans; however, the extent of such differences in the human genome has yet to be fully explored. Here we delineate allelic chromatin modifications and transcriptomes among a broad set of human tissues, enabled by a chromosome-spanning haplotype reconstruction strategy. The resulting large collection of haplotype-resolved epigenomic maps reveals extensive allelic biases in both chromatin state and transcription, which show considerable variation across tissues and between individuals, and allow us to investigate cis-regulatory relationships between genes and their control sequences. Analyses of histone modification maps also uncover intriguing characteristics of cis-regulatory elements and tissue-restricted activities of repetitive elements. The rich data sets described here will enhance our understanding of the mechanisms by which cis-regulatory elements control gene expression programs. PMID:25693566

  9. Solubility of Freon 22 in human blood and lung tissue

    SciTech Connect

    Varene, N.; Choukroun, M.L.; Marthan, R.; Varene, P.

    1989-05-01

    The solubility of Freon 22 in human blood and lung tissue was determined using the chromatographic method of Wagner et al. In normal human blood, the mean Bunsen coefficient of solubility (alpha B) was 0.804 cm3 STPD.cm-3.ATA-1 at 37 degrees C. It increased with hematocrit (Hct) according to the equation alpha B = 0.274 Hct + 0.691. Tissue homogenates were prepared from macroscopically normal lung pieces obtained at thoracotomy from eight patients undergoing resection for lung carcinoma. The Bunsen solubility coefficients were 0.537 +/- 0.068 and 0.635 +/- 0.091 in washed and unwashed lung, respectively. These values can be used in the determination of both cardiac output and pulmonary tissue volume in humans by use of the rebreathing technique.

  10. Differential Diagnosis of Chronic Rhinosinusitis with Nasal Polyps.

    PubMed

    London, Nyall R; Reh, Douglas D

    2016-01-01

    Nasal polyps are semi-translucent mucosal outgrowths of the paranasal sinuses which typically arise in the setting of chronic rhinosinusitis (CRS). Nasal polyps are also associated with asthma, aspirin sensitivity, cystic fibrosis and allergic fungal rhinosinusitis (AFS). The majority of nasal polyps are bilateral and characterized by tissue edema and eosinophil infiltration. Patients with nasal polyps often present with complaints including nasal obstruction, congestion, rhinorrhea or altered sense of smell. The differential diagnosis ranges from benign masses such as schneiderian papilloma, antrochoanal polyp, angiofibroma and encephalocele to malignant neoplasms such as squamous cell carcinoma (SCC), esthesioneuroblastoma, nasal lymphoma and rhabdomyosarcoma. These lesions may have a similar appearance as nasal polyps and particular attention to an alternative diagnosis for nasal polyps should be entertained if the mass is unilateral or congenital in nature. Workup for patients with a unilateral mass should include radiographic imaging, possible biopsy and careful follow-up when appropriate. Here, we review the disease etiology of nasal polyps and describe the approach to the patient with nasal polyps with emphasis on differential diagnosis and workup. PMID:27466841